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• Prokaryotic microbial ecology as a predictor of N. fowleri colonisation. • Ecogenomic methods identify multi-domain trophic interactions. • Selective microbial food sources are required for N. fowleri growth. • Prokaryotes can serve as biological tools to predict sites susceptible to N. fowleri colonisation. Naegleria fowleri has been detected in drinking water distribution systems (DWDS) in Australia, Pakistan and the United States and is the causative agent of the highly fatal disease primary amoebic meningoencephalitis. Previous small scale field studies have shown that Meiothermus may be a potential biomarker for N. fowleri. However, correlations between predictive biomarkers in small sample sizes often breakdown when applied to larger more representative datasets. This study represents one of the largest and most rigorous temporal investigations of Naegleria fowleri colonisation in an operational DWDS in the world and measured the association of Meiothermus and N. fowleri over a significantly larger space and time in the DWDS. A total of 232 samples were collected from five sites over three-years (2016–2018), which contained 29 positive N. fowleri samples. Two specific operational taxonomic units assigned to M. chliarophilus and M. hypogaeus, were significantly associated with N. fowleri presence. Furthermore, inoculation experiments demonstrated that Meiothermus was required to support N. fowleri growth in field-collected biofilms. This validates Meiothermus as prospective biological tool to aid in the identification and surveillance of N. fowleri colonisable sites. [Display omitted] [ABSTRACT FROM AUTHOR]

Objectives: To assess perceptions among breast radiologists regarding optimal breast imaging rotation organization and educational activities for radiology residents.Methods: An IRB-exempt anonymous questionnaire was developed in REDCap and distributed as a member survey email by the Society of Breast imaging to 2188 members June 2019. A form with 33 questions asked questions about opinions related to resident rotation composition, read-out strategies, study/procedure volume, simulation and educational materials specific to breast imaging.Results: A total of 109/2,188 (4.98%) complete survey responses were received. Of the responders, 69/109 (62%) work in academic practice, 16/109 (15%) work in private practice with residents, and 24/109 (22%) work in private practice without residents. There was no significant variation in opinion between those who have >10 years of experience teaching breast imaging 49/109(42.2%) to those with less <10 years' experience 60/109 (55%). A range of opinions is demonstrated regarding the multiple questions asked with more support for diagnostics and procedures on the second and thirds rotations compared to first rotations. There was strong support of in-person staffing, checklists, simulation for ultrasound-guided procedures (91%) and formal training on delivering bad news (90%). Radiology-pathology conferences and faculty-developed teaching files were highest-rated for effective educational tools.Conclusions: The results from this survey show varied opinions regarding perceived best practices for resident breast radiology rotations . Further research is needed to determine training outcomes related to rotation organization. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. [ABSTRACT FROM AUTHOR]

As humanity looks towards expanding activity from low Earth orbit to the Moon and beyond, resource use efficiency and self-sustainability will be critical to ensuring success in the long term. Furthermore, solutions developed for the stringent requirements of space will be equally valuable in meeting sustainability goals here on Earth. Advances in synthetic biology allow us to harness the complex metabolism of life to produce the materials we need in situ. Translating those lessons learned from microbial systems to more carbon-efficient photosynthetic organisms is an area of growing interest. Plants can be engineered to sustainably meet a range of needs, from fuels to materials and medicines. [Display omitted] • Human exploration and habitation in space necessitates and inspires innovation. • Plant photosynthetic capability and scalability brings advantages beyond food production. • Synbio-driven biomanufacturing can support off-Earth human habitation. • It will require robust chassis coupled with genetic circuitry to deliver on-demand production. • This will support the growing closed-environment agriculture and bioeconomy sectors on Earth. [ABSTRACT FROM AUTHOR]

This is a condensed summary of an international multisociety statement on ethics of artificial intelligence (AI) in radiology produced by the ACR, European Society of Radiology, RSNA, Society for Imaging Informatics in Medicine, European Society of Medical Imaging Informatics, Canadian Association of Radiologists, and American Association of Physicists in Medicine. AI has great potential to increase efficiency and accuracy throughout radiology, but it also carries inherent pitfalls and biases. Widespread use of AI-based intelligent and autonomous systems in radiology can increase the risk of systemic errors with high consequence and highlights complex ethical and societal issues. Currently, there is little experience using AI for patient care in diverse clinical settings. Extensive research is needed to understand how to best deploy AI in clinical practice. This statement highlights our consensus that ethical use of AI in radiology should promote well-being, minimize harm, and ensure that the benefits and harms are distributed among stakeholders in a just manner. We believe AI should respect human rights and freedoms, including dignity and privacy. It should be designed for maximum transparency and dependability. Ultimate responsibility and accountability for AI remains with its human designers and operators for the foreseeable future. The radiology community should start now to develop codes of ethics and practice for AI that promote any use that helps patients and the common good and should block use of radiology data and algorithms for financial gain without those two attributes. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate perceptual difference in breast density classification using synthesized mammography (SM) compared with standard or full-field digital mammography (FFDM) for screening.Materials and Methods: This institutional review board-approved, retrospective, multireader study evaluated breast density on 200 patients who underwent baseline screening mammogram during which both SM and FFDM were obtained contemporaneously from June 1, 2016, through November 30, 2016. Qualitative breast density was independently assigned by seven readers initially evaluating FFDM alone. Then, in a separate session, these same readers assigned breast density using synthetic views alone on the same 200 patients. The readers were again blinded to each other's assignment. Qualitative density assessment was based on BI-RADS fifth edition. Interreader agreement was evaluated with κ statistic using 95% confidence intervals. Testing for homogeneity in paired proportions was performed using McNemar's test with a level of significance of .05.Results: For patients across the SM and standard 2-D data set, diagnostic testing with McNemar's test with P = 0.32 demonstrates that the minimal density transitions across FFDM and SM are not statistically significant density shifts. Taking clinical significance into account, only 8 of 200 (4%) patients had clinically significant transition (dense versus not dense). There was substantial interreader agreement with overall κ in FFDM of 0.71 (minimum 0.53, maximum 0.81) and overall SM κ average of 0.63 (minimum 0.56, maximum 0.87).Conclusion: Overall subjective breast density assignment by radiologists on SM is similar to density assignment on standard 2-D mammogram. [ABSTRACT FROM AUTHOR]

The amoeba Naegleria fowleri is the causative agent of the highly fatal disease, primary amoebic meningoencephalitis, and estimated to cause 16 deaths per year in the United States alone. Colonisation of drinking water distribution systems (DWDSs) by the N. fowleri is a significant public health issue. Understanding the factors which enable this pathogen to colonise and thrive in DWDSs is critical for proper management. The microbial ecology within DWDSs may influence the ability of N. fowleri to colonise DWDSs by facilitating the availability of an appropriate food source. Using biofilm samples obtained from operational DWDSs, 16S rRNA amplicon metabarcoding was combined with genus-specific PCR and Sanger sequencing of intracellular associated bacteria from isolated amoeba and their parental biofilms to identify Meiothermus chliarophilus as a potential food source for N. fowleri . Meiothermus was confirmed as a food source for N. fowleri following successful serial culturing of axenic N. fowleri with M. chliarophilus or M. ruber as the sole food source. The ability to identify environmental and ecological conditions favourable to N. fowleri colonisation, including the detection of appropriate food sources such as Meiothermus , could provide water utilities with a predictive tool for managing N. fowleri colonisation within the DWDS. [ABSTRACT FROM AUTHOR]

In screening mammography, accessing prior examination images is crucial for accurate diagnosis and avoiding false-positives. When women visit multiple institutions for their screens, these "outside" examinations must be retrieved for comparison. Traditionally, prior images are obtained by faxing requests to other institutions and waiting for standard mail (film or CD-ROM), which can greatly delay report turnaround times. Recently, advancements in cloud-based image transfer technology have opened up more efficient options for examination transfer between institutions. The objective of this study was to evaluate the effect of cloud-based image transfer on mammography department workflow, time required to obtain prior images, and report turnaround times. Sixty screening examinations requiring prior images were placed into two groups (30 each). The control group used the standard institutional protocol for requesting prior images: faxing requests and waiting for mailed examinations. The experimental group used a cloud-based transfer for both requesting and receiving examinations. The mean number of days between examination request and examination receipt was measured for both groups and compared. The mean number of days from examination request to receipt was 6.08 days (SD 3.50) in the control group compared with 3.16 days (SD 3.95) in the experimental group. Using a cloud-based image transfer to obtain prior mammograms resulted in an average reduction of 2.92 days (P = .0361; 95% confidence interval 0.20-5.65) between examination request and receipt. This improvement in system efficiency is relevant for interpreting radiologists working to improve reporting times and for patients anxious to receive their mammography results. [ABSTRACT FROM AUTHOR]

Introduction: Extensive physiologic changes occur in the breasts during pregnancy and lactation. Additionally, several specific benign lesions are also common in pregnant and lactating patients. These changes and lesions have characteristic imaging appearances and findings.Objective: This article provides an image-rich educational review of typical and atypical benign imaging findings in pregnant and lactating patients. The discussion also includes basic imaging protocol considerations and explores management options.Conclusion: An understanding of the typical and atypical imaging appearance of physiological changes and specific benign lesions occurring in pregnancy and lactation is essential for appropriate patient care and management. [ABSTRACT FROM AUTHOR]

Global incidence of primary amoebic meningoencephalitis cases associated with domestic drinking water is increasing. The need for understanding disinfectant regimes capable of eliminating the causative microorganism, Naegleria fowleri, from bulk water and pipe wall biofilms is critical. This field study demonstrated the successful elimination of N. fowleri from the bulk water and pipe wall biofilm of a persistently colonised operational drinking water distribution system (DWDS), and the prevention of further re-colonisation. A new chlorination unit was installed along the pipe line to boost the free chlorine residual to combat the persistence of N. fowleri . Biofilm and bulk water were monitored prior to and after re-chlorination (RCl), pre-rechlorination (pre-RCl) and post-rechlorination (post-RCl), respectively, for one year. A constant free chlorine concentration of > 1 mg/L resulted in the elimination of N. fowleri from both the bulk water and biofilm at the post-RCl site. Other amoeba species were detected during the first two months of chlorination, but all amoebae were eliminated from both the bulk water and biofilm at post-RCl after 60 days of chlorination with free chlorine concentrations > 1 mg/L. In addition, a dynamic change in the biofilm community composition and a four log reduction in biofilm cell density occurred post-RCl. The pre-RCl site continued to be seasonally colonised by N. fowleri , but the constant free chlorine residual of > 1 mg/L prevented N. fowleri from recolonising the bulk and pipe wall biofilm at the post-RCl site. To our knowledge, this is the first study to demonstrate successful removal of N. fowleri from both the bulk and pipe wall biofilm and prevention of re-colonisation of N. fowleri in an operational DWDS. The findings of this study are of importance to water utilities in addressing the presence of N. fowleri and other amoeba in susceptible DWDSs. [ABSTRACT FROM AUTHOR]

DNA-derived measurements of biological composition have the potential to produce data covering all of life, and provide a tantalizing proposition for researchers and managers. We used metabarcoding to compare benthic eukaryote composition from five estuaries of varying condition. In contrast to traditional studies, we found biotic richness was greatest in the most disturbed estuary, with this being due to the large volume of extraneous material (i.e. run-off from aquaculture, agriculture and other catchment activities) being deposited in the system. In addition, we found strong correlations between composition and a number of environmental variables, including nutrients, pH and turbidity. A wide range of taxa responded to these environmental gradients, providing new insights into their sensitivities to natural and anthropogenic stressors. Metabarcoding has the capacity to bolster current monitoring techniques, enabling the decisions regarding ecological condition to be based on a more holistic view of biodiversity. [ABSTRACT FROM AUTHOR]

In the Colorado Piedmont, talus flatiron chronosequences are associated with buttes that consist of erodible arkosic sandstone and resistant caprock. Following the removal of the caprock, some buttes evolve into crater-like relict slope rings resulting from the differential erosion of the soft bedrock in the core of the hills. These unique landforms are only documented in the Colorado Piedmont. Their development is attributed to the unusually high erodibility contrast between the low-cohesion sandy bedrock and the bouldery colluvial armor. The talus flatiron sequences and relict slope rings mapped in the three studied areas record alternating periods of accumulation and incision in the slopes that are likely controlled by changes in moisture availability and vegetation cover density. The obtained OSL dates place slope accumulation phases at > 124 ka, and ca. 73 ka, 50–40 ka, 15 ka, and 10–6 ka. A comparison of these geochronological data with paleoclimatic records from the region suggests that colluvium deposition occurred during periods of denser vegetation cover, which are controlled by climate changes. Further investigations, including additional and more accurate geochrological data from the relict slopes, will help to better understand the paleoclimatic significance of these largely unknown morphostratigraphic features. [ABSTRACT FROM AUTHOR]

IT in health care has evolved rapidly over the past 20 years. The rise of the computer is at the core of these changes. Most agree that although these technologies have revolutionized the practice of medicine, they have additionally fostered a data revolution that is simultaneously useful and disruptive. The effective use and implementation of the right IT tools are critical to the success of the imaging profession. This article serves as a guideline to radiologists on how to build an effective IT division within an imaging enterprise from the perspective of leadership, management, and human resources. We address the process for building an IT team from the ground up and also provide recommendations for modifying an existing IT group to make it more effective. Paramount to this discussion is the concept of the imaging informatics professional and the advantage this type of training brings to a radiology department. In addition, we focus on the critical role of the physician informaticist as a liaison to bridge gaps among the IT, medical, and administrative functions in an organization. [ABSTRACT FROM AUTHOR]

Purpose: Decision support systems for radiologists can provide information during image interpretation that may efficiently improve diagnostic accuracy and increase radiologists'' confidence. However, most decision support systems require radiologists to exit PACS, which may deter busy radiologists from pursuing decision support. The purpose of this study was to determine whether radiologists would use a PACS-integrated decision support tool more frequently than an equivalent nonintegrated system. Methods: Forty-eight radiology residents were randomly assigned to one of two groups: the control group was provided access to a radiology clinical decision support tool via Web access, which required the resident to launch a Web browser from a desktop icon and then log in to the decision support application. The experimental group was provided access to the same tool but was allowed to launch from a PACS-integrated portal with automated login and authentication. Halfway through the 10-month study period, the groups were switched. The main outcome measure was the average number of decision support sessions initiated each month over the study period. Results: The experimental (integrated) group had higher use than the control (nonintegrated) group by a factor of 3.0 (P < .05). When integrated access was removed from the experimental group, their use fell by 52%. When integrated access was granted to the control group, their use rose by only 20%. Conclusion: Integration with PACS improves radiologists'' use of clinical decision support tools. Integrated access is critical at the time of initial deployment, or acceptance of the decision support tools may be undermined. [Copyright &y& Elsevier]

Background: Validated prediction scores are required to assess the risks of end-stage renal disease (ESRD) and death in individuals with chronic kidney disease (CKD). Study Design: Prospective cohort study with validation in a separate cohort. Setting & Participants: Cox regression was used to assess the relevance of baseline characteristics to risk of ESRD (mean follow-up, 4.1 years) and death (mean follow-up, 6.0 years) in 382 patients with stages 3-5 CKD not initially on dialysis therapy in the Chronic Renal Impairment in Birmingham (CRIB) Study. Resultant risk prediction equations were tested in a separate cohort of 213 patients with CKD (the East Kent cohort). Factors: 44 baseline characteristics (including 30 blood and urine assays). Outcomes: ESRD and all-cause mortality. Results: In the CR IB cohort, 190 patients reached ESRD (12.1%/y) and 150 died (6.5%/y). Each 30% lower baseline estimated glomerular filtration rate was associated with a 3-fold higher ESRD rate and a 1.3-fold higher death rate. After adjustment for each other, only baseline creatinine level, serum phosphate level, urinary albumin-creatinine ratio, and female sex remained strongly (P < 0.01) predictive of ESRD. For death, age, N-terminal pro-brain natriuretic peptide, troponin T level, and cigarette smoking remained strongly predictive of risk. Using these factors to predict outcomes in the East Kent cohort yielded an area under the receiver operating characteristic curve (ie, C statistic) of 0.91 (95% CIl, 0.87-0.96) for ESRD and 0.82 (95% CI, 0.75-0.89) for death. Limitations: Other important factors may have been missed because of limited study power. Conclusions: Simple laboratory measures of kidney and cardiac function plus age, sex, and smoking history can be used to help identify patients with CKD at highest risk of ESRD and death. Larger cohort studies are required to further validate these results. [ABSTRACT FROM AUTHOR]

Rationale and Objectives: To determine whether emergency department (ED) preliminary reports rendered by subspecialist attending radiologists who are reading outside their field of expertise are more accurate than reports rendered by radiology residents, and to compare error rates between radiologists and nonradiologists in the ED setting. Materials and Methods: The study was performed at a large academic medical center with a busy ED. An electronic preliminary report generator was used in the ED to capture preliminary interpretations rendered in a clinical setting by radiology residents, junior attendings (within 2 years of taking their oral boards), senior attendings, and ED clinicians between August 1999 and November 2004. Each preliminary report was later reviewed by a final interpreting radiologist, and the preliminary interpretation was adjudicated for the presence of substantial discordances, defined as a difference in interpretation that might immediately impact the care of the patient. Of the 612,890 preliminary reports in the database, 65,780 (11%) met inclusion criteria for this study. A log-linear analysis was used to assess the effects of modality and type of author on preliminary report error rates. Results: ED clinicians had significantly higher error rates when compared with any type of radiologist, regardless of modality. Within the radiologists, residents and junior attendings had lower error rates than did senior attendings, but the differences were not statistically significant. Conclusion: Subspecialized attending radiologists who interpret ED examinations outside their area of expertise have error rates similar to those of radiology residents. Nonradiologists have significantly higher error rates than radiologists and radiology residents when interpreting examinations in the ED. [Copyright &y& Elsevier]

Summary: The E-Cadherin-catenin complex plays a critical role in epithelial cell-cell adhesion, polarization, and morphogenesis. Here, we have analyzed the mechanism of Drosophila E-Cadherin (DE-Cad) localization. Loss of function of the Drosophila exocyst components sec5, sec6, and sec15 in epithelial cells results in DE-Cad accumulation in an enlarged Rab11 recycling endosomal compartment and inhibits DE-Cad delivery to the membrane. Furthermore, Rab11 and Armadillo interact with the exocyst components Sec15 and Sec10, respectively. Our results support a model whereby the exocyst regulates DE-Cadherin trafficking, from recycling endosomes to sites on the epithelial cell membrane where Armadillo is located. [Copyright &y& Elsevier]

The primary systemic vasculitides are a rare group of inflammatory disorders, where damage is directed against the blood vessels. They range in severity from acute self-limiting illness to chronic life and organ threatening diseases requiring long-term treatment with toxic immunosuppressive regimes. None of them have specific tests and few have hard diagnostic criteria. This review summarises the gastrointestinal features of these diseases, along with their general clinical and epidemiological features and the evidence available to guide in their management. [Copyright &y& Elsevier]

slug gene expression is associated with the specification and migration of neural crest cells in the African clawed frog Xenopus laevis. We provide evidence that the protein Ying-Yang 1 (YY1) regulates the slug gene expression both indirectly and directly, via a YY1 ciselement in the slug promoter, during Xenopus development. The ability of the YY1 to bind this YY1 cis-element was confirmed by electromobility shift assays and reporter assays. YY1 was detected in the nuclei of ectodermai cells contemporaneously with the process of neural crest specification. The injection of anti-YY1 morpholino, which targeted both YY1α and YY1β gene products, depleted YY1 expression below 20% and was lethal at gastrulation. Sublethal depletion of YY1 reduced the length of the anterior-posterior axis and severely inhibited the expression of the neural marker Nrp1 and of the slug gene. Overexpression of YY1 or mutation of the YY1 cis-element reduced the restricted spatial expression of the slug reporter gene in the neural ectoderm border and provoked its expression in the nonneural ectoderm. Chromatin immunoprecipitation indicated that endogenous YY1 interacts directly with the YY1 cis-element of the endogenous slug gene and with the slug gene reporter sequence injected into embryos. The results suggest that YY1 is essential for Xenopus development; is necessary for neural ectoderm differentiation, a prerequisite for neural crest specification; and restricts which cells can form neural crest mesenchyme through directly blocking slug gene activity. [ABSTRACT FROM AUTHOR]

During the First Gulf War (1991) a large number of oil wells were destroyed and oil fires subsequently extinguished with seawater. As a result Kuwait's sparse fresh groundwater resources were severely contaminated with crude oil. Since then limited research has focused on the microbial community ecology of the groundwater and their impact on the associated contamination. Here, the microbial community ecology (bacterial, archaeal and eukaryotic) and how it relates to the characteristics of the hydrocarbon contaminants were examined for the first time since the 1991 event. This study was conducted using 15 wells along the main groundwater flow direction and detected several potential hydrocarbon degrading microorganisms such as Hyphomicrobiaceae , Porphyromonadaceae and Eurotiomycetes. The beta diversity of the microbial communities correlated significantly with total petroleum hydrocarbon (TPH) concentrations and salinity. The TPH consisted mainly of polar compounds present as an unresolved complex mixture (UCM) of a highly recalcitrant nature. Based on the proportions of TPH to dissolved organic carbon (DOC), the results indicate that some minor biodegradation has occurred within highly contaminated aquifer zones. However, overall the results from this study suggest that the observed variations in TPH concentrations among the sampled wells are mainly induced by mixing/dilution with pristine groundwater rather than by biodegradation of the contaminants. The findings make an important contribution to better understand the fate of the groundwater pollution in Kuwait, with important implications for the design of future remediation efforts. Image 1 • Bruckberger et al. Highlights. • First investigation of microbial communities in 1st Gulf War impacted aquifers. • Community structure correlated with contaminant (TPH & EC) concentrations. • Biodegradation extent of the recalcitrant contaminant has remained minimal. • Contaminant more impacted by dilution rather than significant biodegradation. [ABSTRACT FROM AUTHOR]

Abstract: 4-aminopyridine (4-AP) is an orphan drug in the United States. It enhances neuronal conduction at synapses and is indicated in the treatment of selected neuromuscular disorders, including multiple sclerosis and myasthenia gravis, among others. Its documented toxicity generally has been limited to central nervous system (CNS) hyperexcitation and gastrointestinal upset. In this case, a 56-year-old man accidentally overdosed on an unknown amount of generic 4-AP. This history was unknown by his family and unavailable to initial providers. Approximately 1 h after ingestion, his son found him diaphoretic, vomiting, and having unintelligible speech. In the ensuing 2–3 h, the patient became moderately hypothermic (32.8°C; 91°F), developed atrial fibrillation with a rapid ventricular response, and had neurological changes that were confused with an acute cerebrovascular accident. After a 36-h stay in the intensive care unit that included mechanical ventilation, cardioversion, passive rewarming, and an extensive medical workup, the patient recovered without sequelae. After extubation he stated that he thought he may have ingested too much 4-AP after rubbing a large amount of it against a sore tooth to take advantage of its local analgesic properties. This case of 4-AP overdose resulting in atrial fibrillation with rapid ventricular response, hypothermia, and acute neurological changes mistaken for an acute cerebrovascular accident is an unusual one. This case shows that overdose of 4-AP can cause or mimic several serious medical conditions, and that a detailed history and physical examination are essential for uncovering unusual diagnoses. [Copyright &y& Elsevier]

Current clinical abdominal imaging arrays are designed to maximize angular field of view rather than the extent of the coherent aperture. We illustrate, in ex vivo experiments, the use of a large effective aperture to perform high-resolution imaging, even in the presence of abdominal wall-induced acoustic clutter and aberration. Point and lesion phantom targets were imaged through a water path and through three excised cadaver abdominal walls to create different clinically relevant clutter effects with matched imaging targets. A 7.36-cm effective aperture was used to image the targets at a depth of 6.4 cm, and image quality metrics were measured over a range of aperture sizes using synthetic aperture techniques. In all three cases, although degradation compared with the control was observed, lateral resolution improved with increasing aperture size without loss of contrast. Spatial compounding of the large-aperture data drastically improved lesion detectability and produced contrast-to-noise ratio improvements of 83%-106% compared with the large coherent aperture. These studies indicate the need for the development of large arrays for high-resolution abdominal diagnostic imaging. [ABSTRACT FROM AUTHOR]

Pregnancy in patients with anti-neutrophil cytoplasm antibody-associated vasculitis is reportedly associated with a high risk of fetal and maternal complications. Here we describe the outcome of pregnancies in patients with granulomatosis with polyangiitis and microscopic polyangiitis at five centers in the United Kingdom using a retrospective case review of all women who became pregnant following diagnosis. We report 15 pregnancies in 13 women resulting in 15 live births including one twin pregnancy and 13 singleton pregnancies. One patient had an unplanned pregnancy and a first trimester miscarriage while taking methotrexate. All other pregnancies were planned following a minimum of 6 months clinical remission. Eleven successful pregnancies were delivered vaginally at full term, whereas three were delivered by cesarean section. All infants were healthy with no neonatal complications on their initial health check within the first 24 h of delivery and no evidence of neonatal vasculitis. One relapse occurred during pregnancy and was successfully treated with an increased dose of azathioprine and corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. One patient developed tracheal crusting and subglottic stenosis of infective etiology in the third trimester requiring tracheal debridement post delivery. No patient had a relapse in the first 12 months postpartum. Thus, successful pregnancy outcomes can occur following planned pregnancy in women in sustained remission on non-teratogenic therapies. [ABSTRACT FROM AUTHOR]

Abstract: A series of TRPV1 agonists with amide, reverse amide, and thiourea groups in the B-region and their corresponding α-methylated analogues were investigated. Whereas the α-methylation of the amide B-region enhanced the binding affinities and potencies as agonists, that of the reverse amide and thiourea led to a reduction in receptor affinity. The analysis indicated that proper hydrogen bonding as well as steric effects in the B-region are critical for receptor binding. [Copyright &y& Elsevier]

Abstract: On the basis of the previous lead N-4-t-butylbenzyl 2-(3-fluoro-4-methylsulfonylaminophenyl) propanamide (3) as a potent TRPV1 antagonist, structure–activity relationships for the B (propanamide part) and C-region (4-t-butylbenzyl part) have been investigated for rTRPV1 in CHO cells. The B-region was modified with dimethyl, cyclopropyl and reverse amides and then the C-region was replaced with 4-substituted phenyl, aryl alkyl and diaryl alkyl derivatives. Among them, compound 50 showed high binding affinity with K i =21.5nM, which was twofold more potent than 3 and compound 54 exhibited potent antagonism with K i(ant) =8.0nM comparable to 3. [Copyright &y& Elsevier]

Abstract: Structure–activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54 S versus 54 R ). A docking study of 54 S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency. [Copyright &y& Elsevier]

Abstract: This paper presents a novel design and the prototyped solar cooking stove which uses a large Fresnel lens for the concentration of sunlight. The technology demonstrates high safety and efficiency of solar cooking and heating using Fresnel lenses which are low cost and available from off-the-shelf. The stove has a fixed heat-receiving area located at the focal point of the lens. The sunlight tracking system rotates the Fresnel lens about its focal point in both zenith and azimuth angles. The tracking is accomplished through a revolving motion of two rotation arms that hold the lens and a horizontal rotation of a platform that the lens system stands on. The rotation of the arms tracks the sunlight in zenith plane, while the rotation of the platform tracks in the azimuth plane. Since the solar tracking allows the Fresnel lens to concentrate sunlight to a fixed small heat-receiving area, relatively low heat loss and high energy efficiency is made possible. The heat is used to maintain a stovetop surface at temperatures around as high as 300 °C, which is practical for cooking applications in a very safe, user-friendly, and convenient manner. The system also demonstrates the possibility of transferring heat using a working fluid for indoor heating and cooking. Wider applications using the system for solar thermal collection and utilization are also undergoing development. [ABSTRACT FROM AUTHOR]

Abstract: Colorectal cancer (CRC) is a major cause of cancer-related morbidity and mortality. Molecular imaging using positron emission tomography (PET) is now an integral part of multidisciplinary cancer care. In this review, we discuss the role of PET in CRC including well established indications in the assessment of recurrent disease and emerging applications such as initial staging, monitoring therapy efficacy and using PET for radiotherapy planning. With rapid advancement in imaging technology, we also discuss the future potential of combining PET and magnetic resonance imaging and the use of novel radiotracers. [Copyright &y& Elsevier]

Abstract: A series of non-vanillyl resiniferatoxin analogues, having 4-methylsulfonylaminophenyl and fluorophenyl moieties as vanillyl surrogates, have been investigated as ligands for rat TRPV1 heterologously expressed in Chinese hamster ovary cells. Although lacking the metabolically problematic 4-hydroxy substituent on the A-region phenyl ring, the compounds retained substantial agonist potency. Indeed, the 3-methoxy-4-methylsulfonylaminophenyl analog (1) was modestly (2.5-fold) more potent than RTX, with an EC50 =0.106nM. Further, it resembled RTX in its kinetics and pattern of stimulation of the levels of intracellular calcium in individual cells, as revealed by imaging. Compound 1 displayed modestly enhanced in vitro stability in rat liver microsomes and in plasma, suggesting that it might be a pharmacokinetically more favorable surrogate of resiniferatoxin. Molecular modeling analyses with selected analogues provide evidence that the conformational differences could affect their binding affinities, especially for the ester versus amide at the B-region. [Copyright &y& Elsevier]