Dust-free quasars in the early Universe

The most distant quasars known, at redshifts z=6, generally have properties indistinguishable from those of lower-redshift quasars in the rest-frame ultraviolet/optical and X-ray bands. This puzzling result suggests that these distant quasars are evolved objects even though the Universe was only seven per cent of its current age at these redshifts. Recently one z=6 quasar was shown not to have any detectable emission from hot dust, but it was unclear whether that indicated different hot-dust properties at high redshift or if it is simply an outlier. Here we report the discovery of a second quasar without hot-dust emission in a sample of 21 z=6 quasars. Such apparently hot-dust-free quasars have no counterparts at low redshift. Moreover, we demonstrate that the hot-dust abundance in the 21 quasars builds up in tandem with the growth of the central black hole, whereas at low redshift it is almost independent of the black hole mass. Thus z=6 quasars are indeed at an early evolutionary stage, with rapid mass accretion and dust formation. The two hot-dust-free quasars are likely to be first-generation quasars born in dust-free environments and are too young to have formed a detectable amount of hot dust around them.Comment: To be published in Nature on the 18 March 2010

Benefits of robotic cystectomy with intracorporeal diversion for patients with low cardiorespiratory fitness: A prospective cohort study

BACKGROUND: Patients undergoing radical cystectomy have associated comorbidities resulting in reduced cardiorespiratory fitness. Preoperative cardiopulmonary exercise testing (CPET) measures including anaerobic threshold (AT) can predict major adverse events (MAE) and hospital length of stay (LOS) for patients undergoing open and robotic cystectomy with extracorporeal diversion. Our objective was to determine the relationship between CPET measures and outcome in patients undergoing robotic radical cystectomy and intracorporeal diversion (intracorporeal robotic assisted radical cystectomy [iRARC]). METHODS: A single institution prospective cohort study in patients undergoing iRARC for muscle invasive and high-grade bladder cancer. Inclusion: patients undergoing standardised CPET before iRARC. Exclusions: patients not consenting to data collection. Data on CPET measures (AT, ventilatory equivalent for carbon dioxide [VE/VCO2] at AT, peak oxygen uptake [VO2]), and patient demographics prospectively collected. Outcome measurements included hospital LOS; 30-day MAE and 90-day mortality data, which were prospectively recorded. Descriptive and regression analyses were used to assess whether CPET measures were associated with or predicted outcomes. RESULTS: From June 2011 to March 2015, 128 patients underwent radical cystectomy (open cystectomy, n = 17; iRARC, n = 111). A total of 82 patients who underwent iRARC and CPET and consented to participation were included. Median (interquartile range): age = 65 (58–73); body mass index = 27 (23–30); AT = 10.0 (9–11), Peak VO2 = 15.0 (13–18.5), VE/VCO2 (AT) = 33.0 (30–38). 30-day MAE = 14/111 (12.6%): death = 2, multiorgan failure = 2, abscess = 2, gastrointestinal = 2, renal = 6; 90-day mortality = 3/111 (2.7%). AT, peak VO2, and VE/VCO2 (at AT) were not significant predictors of 30-day MAE or LOS. The results are limited by the absence of control group undergoing open surgery. CONCLUSIONS: Poor cardiorespiratory fitness does not predict increased hospital LOS or MAEs in patients undergoing iRARC. Overall, MAE and LOS comparable with other series

Differential development of neuronal physiological responsiveness in two human neural stem cell lines

Background: Neural stem cells (NSCs) are powerful research tools for the design and discovery of new approaches to neurodegenerative disease. Overexpression of the myc family transcription factors in human primary cells from developing cortex and mesencephalon has produced two stable multipotential NSC lines (ReNcell VM and CX) that can be continuously expanded in monolayer culture.Results: In the undifferentiated state, both ReNcell VM and CX are nestin positive and have resting membrane potentials of around -60 mV but do not display any voltage-activated conductances. As initially hypothesized, using standard methods (stdD) for differentiation, both cell lines can form neurons, astrocytes and oligodendrocytes according to immunohistological characteristics. However it became clear that this was not true for electrophysiological features which designate neurons, such as the firing of action potentials. We have thus developed a new differentiation protocol, designated 'pre-aggregation differentiation' (preD) which appears to favor development of electrophysiologically functional neurons and to lead to an increase in dopaminergic neurons in the ReNcell VM line. In contrast, the protocol used had little effect on the differentiation of ReNcell CX in which dopaminergic differentiation was not observed. Moreover, after a week of differentiation with the preD protocol, 100% of ReNcell VM featured TTX-sensitive Na+-channels and fired action potentials, compared to 25% after stdD. Currents via other voltage-gated channels did not appear to depend on the differentiation protocol. ReNcell CX did not display the same electrophysiological properties as the VM line, generating voltage-dependant K+ currents but no Na+ currents or action potentials under either stdD or preD differentiation.Conclusion: These data demonstrate that overexpression of myc in NSCs can be used to generate electrophysiologically active neurons in culture. Development of a functional neuronal phenotype may be dependent on parameters of isolation and differentiation of the cell lines, indicating that not all human NSCs are functionally equivalent

Blood Transfusion Requirement and not Preoperative Anaemia is associated with Perioperative Complications following Intracorporeal Robotic Assisted Radical Cystectomy

OBJECTIVES: To assess the prevalence of preoperative anaemia and the impact of preoperative anaemia and blood transfusion requirement on 30- and 90-day complications in a cohort of patients undergoing robotic assisted radical cystectomy with intracorporeal urinary diversion (iRARC). PATIENTS & METHODS: IRARC was performed on 166 patients between June 2011-March 2016. Prospective data was collected for patient demographics, clinical and pathological characteristics, perioperative variables, transfusion requirements and hospital length of stay. Thirty- and 90-day complications were classified according to the modified Memorial Sloan-Kettering Cancer Center Clavian-Dindo system. RESULTS: Preoperative anaemia was common (43.4%) and greatest in patients receiving neoadjuvant chemotherapy (48.6%) (p<0.001). Patients with preoperative anaemia were significantly more likely to have an Ileal conduit (p=0.033), higher cystectomy stage (≥pT3) (p=0.028) and a lower lymph node yield (p=0.031). Preoperative anaemia was not associated with increased perioperative morbidity but was associated with the need for blood transfusion (p=0.001). Blood transfusion was required in 20.4% of patients with intraoperative and postoperative blood transfusion rate was 10.2% and 13.9% respectively. The 30-day all complication rate and 30-day major complication rate was 55.4% and 15.7% respectively while 90-day all complication rate and 90-day major complication rate were 65.7% and 19.3% respectively. Intraoperative blood transfusion was not associated with increased complications but postoperative blood transfusion requirement was independently associated with perioperative morbidity: all 30 day complications (p=0.003), all 90-day complications (p=0.009) and 90-day major complications (p=0.004). CONCLUSION: The presence of preoperative anaemia in patients undergoing iRARC is not associated with increased surgical risk although preoperative anaemic patients were significantly more likely to require blood transfusion. Blood transfusion requirement and specifically postoperative blood transfusion is independently associated with perioperative morbidity and is an important factor for the optimisation of postoperative outcomes

A Comprehensive Workflow for General-Purpose Neural Modeling with Highly Configurable Neuromorphic Hardware Systems

In this paper we present a methodological framework that meets novel requirements emerging from upcoming types of accelerated and highly configurable neuromorphic hardware systems. We describe in detail a device with 45 million programmable and dynamic synapses that is currently under development, and we sketch the conceptual challenges that arise from taking this platform into operation. More specifically, we aim at the establishment of this neuromorphic system as a flexible and neuroscientifically valuable modeling tool that can be used by non-hardware-experts. We consider various functional aspects to be crucial for this purpose, and we introduce a consistent workflow with detailed descriptions of all involved modules that implement the suggested steps: The integration of the hardware interface into the simulator-independent model description language PyNN; a fully automated translation between the PyNN domain and appropriate hardware configurations; an executable specification of the future neuromorphic system that can be seamlessly integrated into this biology-to-hardware mapping process as a test bench for all software layers and possible hardware design modifications; an evaluation scheme that deploys models from a dedicated benchmark library, compares the results generated by virtual or prototype hardware devices with reference software simulations and analyzes the differences. The integration of these components into one hardware-software workflow provides an ecosystem for ongoing preparative studies that support the hardware design process and represents the basis for the maturity of the model-to-hardware mapping software. The functionality and flexibility of the latter is proven with a variety of experimental results

A cohort study of 30 day mortality after NON-EMERGENCY surgery in a COVID-19 cold site

BACKGROUND: Two million non-emergency surgeries are being cancelled globally every week due to the COVID-19 pandemic, which will have a major impact on patients and healthcare systems. METHODS: During the peak of the pandemic in the United Kingdom, we set up a multicentre cancer network amongst 14 National Health Service institutions, performing urological, thoracic, gynaecological and general surgical urgent and cancer operations at a central COVID-19 cold site. This is a cohort study of 500 consecutive patients undergoing surgery in this network. The primary outcome was 30-day mortality from COVID-19. Secondary outcomes included all-cause mortality and post-operative complications at 30-days. RESULTS: 500 patients underwent surgery with median age 62.5 (IQR 51-71). 65% were male, 60% had a known diagnosis of cancer and 61% of surgeries were considered complex or major. No patient died from COVID-19 at 30-days. 30-day all-cause mortality was 3/500 (1%). 10 (2%) patients were diagnosed with COVID-19, 4 (1%) with confirmed laboratory diagnosis and 6 (1%) with probable COVID-19. 33/500 (7%) of patients developed Clavien-Dindo grade 3 or higher complications, with 1/33 (3%) occurring in a patient with COVID-19. CONCLUSION: It is safe to continue cancer and urgent surgery during the COVID-19 pandemic with appropriate service reconfiguration

Middle Segment Pancreatectomy: A Useful Tool in the Management of Pancreatic Neoplasms

Small, benign, or low-grade malignant tumors located in the neck of the pancreas are usually treated with enucleation. However, if enucleation is too risky because of possible damage of the main pancreatic duct, standard pancreatic resections are performed. Such operations can lead to impaired long-term exocrine–endocrine function. Middle segment pancreatectomy consists of a limited resection of the midportion of the pancreas and can be performed in selected patients affected by tumors of the pancreatic neck. Middle segment pancreatectomy is a safe and feasible procedure for treating tumors of the pancreatic neck; in experienced hands it is associated with no mortality but with high morbidity, even if the rate of “clinical” pancreatic fistula is about 20%. Moreover, it allows a surgeon to preserve pancreatic parenchyma and consequently long-term endocrine and exocrine pancreatic function

Biological monitoring of pesticide exposures in residents living near agricultural land

<p>Abstract</p> <p>Background</p> <p>There is currently a lack of reliable information on the exposures of residents and bystanders to pesticides in the UK. Previous research has shown that the methods currently used for assessing pesticide exposure for regulatory purposes are appropriate for farm workers <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>. However, there were indications that the exposures of bystanders may sometimes be underestimated. The previous study did not collect data for residents. Therefore, this study aims to collect measurements to determine if the current methods and tools are appropriate for assessing pesticide exposure for residents living near agricultural fields.</p> <p>Methods/design</p> <p>The study will recruit owners of farms and orchards (hereafter both will be referred to as farms) that spray their agricultural crops with certain specified pesticides, and which have residential areas in close proximity to these fields. Recruited farms will be asked to provide details of their pesticide usage throughout the spray season. Informed consenting residents (adults (18 years and over) and children(aged 4-12 years)) will be asked to provide urine samples and accompanying activity diaries during the spraying season and in additionfor a limited number of weeks before/after the spray season to allow background pesticide metabolite levels to be determined. Selected urine samples will be analysed for the pesticide metabolites of interest. Statistical analysis and mathematical modelling will use the laboratory results, along with the additional data collected from the farmers and residents, to determine systemic exposure levels amongst residents. Surveys will be carried out in selected areas of the United Kingdom over two years (2011 and 2012), covering two spraying seasons and the time between the spraying seasons.</p> <p>Discussion</p> <p>The described study protocol was implemented for the sample and data collection procedures carried out in 2011. Based on experience to date, no major changes to the protocol are anticipated for the 2012 spray season although the pesticides and regional areas for inclusion in 2012 are still to be confirmed.</p

The genomes of two key bumblebee species with primitive eusocial organization

Background: The shift from solitary to social behavior is one of the major evolutionary transitions. Primitively eusocial bumblebees are uniquely placed to illuminate the evolution of highly eusocial insect societies. Bumblebees are also invaluable natural and agricultural pollinators, and there is widespread concern over recent population declines in some species. High-quality genomic data will inform key aspects of bumblebee biology, including susceptibility to implicated population viability threats. Results: We report the high quality draft genome sequences of Bombus terrestris and Bombus impatiens, two ecologically dominant bumblebees and widely utilized study species. Comparing these new genomes to those of the highly eusocial honeybee Apis mellifera and other Hymenoptera, we identify deeply conserved similarities, as well as novelties key to the biology of these organisms. Some honeybee genome features thought to underpin advanced eusociality are also present in bumblebees, indicating an earlier evolution in the bee lineage. Xenobiotic detoxification and immune genes are similarly depauperate in bumblebees and honeybees, and multiple categories of genes linked to social organization, including development and behavior, show high conservation. Key differences identified include a bias in bumblebee chemoreception towards gustation from olfaction, and striking differences in microRNAs, potentially responsible for gene regulation underlying social and other traits. Conclusions: These two bumblebee genomes provide a foundation for post-genomic research on these key pollinators and insect societies. Overall, gene repertoires suggest that the route to advanced eusociality in bees was mediated by many small changes in many genes and processes, and not by notable expansion or depauperation

Extragenital Müllerian adenosarcoma with pouch of Douglas location

Background: Of all female genital tract tumors, 1-3% are stromal malignancies. In 8-10% of cases, these are represented by Mullerian adenosarcoma an extremely rare tumor characterized by a stromal component of usually low-grade malignancy and by a benign glandular epithelial component. Variant that arises in the pouch of Douglas is scarcely mentioned in the medical literature.Case Presentation: A 49-year-old para-0 woman, was seen at our OB/GYN-UNIT because she complained vaguely of pelvic pain. She had a mass of undefined nature in the pouch of Douglas. A simple excision of the mass showed low-grade Mullerian adenosarcoma with areas of stromal overgrowth. One and a half year after surgery, at another hospital, a mass was detected in the patient's posterior vaginal fornix and removed surgically. Six months later she came back to our observation with vaginal bleeding and mass in the vaginal fornix. We performed radical surgery. The pathological examination showed recurrent adenosarcoma. Surgical treatment was supplemented by radiation therapy.Conclusions: The case of Mullerian adenosarcoma reported here is the third known so far in the literature that was located in the pouch of Douglas. To date, only two other such cases have been reported, including one resulting from neoplastic degeneration of an endometriotic cyst