1,088 research outputs found
The Cancer Hub Approach for Upper Gastrointestinal Surgery During COVID-19 Pandemic: Outcomes from a UK Cancer Centre.
BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic caused unprecedented disruption to global healthcare delivery. In England, the majority of elective surgery was postponed or cancelled to increase intensive care capacity. Our unit instituted the 'RM Partners Cancer Hub' at the Royal Marsden Hospital in London, to deliver ongoing cancer surgery in a 'COVID-lite' setting. This article describes the operational set-up and outcomes for upper gastrointestinal (UGI) cancer resections performed during this period. METHODS: From April 2020 to April 2021, the Royal Marsden Hospital formed the RM Partners Cancer Hub. This approach was designed to coordinate resources and provide as much oncological treatment as feasible for patients across the RM Partners West London Cancer Alliance. A UGI surgical case prioritisation strategy, along with strict infection control pathways and pre-operative screening protocols, was adopted. RESULTS: A total of 231 patients underwent surgery for confirmed or suspected UGI cancer during the RM Partners Cancer Hub, with 213 completed resections and combined 90-day mortality rate of 3.5%. Good short-term survival outcomes were demonstrated with 2-year disease free survival (DFS) and overall survival (OS) for oesophageal (70.8% and 72.9%), gastric (66.7% and 83.3%) and pancreatic cancer resections (68.0% and 88.0%). One patient who developed perioperative COVID-19 during the RM Partners Cancer Hub operation made a full recovery with no lasting clinical sequelae. CONCLUSION: Our experience demonstrates that the RM Partners Cancer Hub approach is a safe strategy for continuing upper gastrointestinal (GI) resectional surgery during future periods of healthcare service disruption
Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae
Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity
Automated Identification of Acute Hepatitis B Using Electronic Medical Record Data to Facilitate Public Health Surveillance
Automatic identification of notifiable diseases from electronic medical records can potentially improve the timeliness and completeness of public health surveillance. We describe the development and implementation of an algorithm for prospective surveillance of patients with acute hepatitis B using electronic medical record data.Initial algorithms were created by adapting Centers for Disease Control and Prevention diagnostic criteria for acute hepatitis B into electronic terms. The algorithms were tested by applying them to ambulatory electronic medical record data spanning 1990 to May 2006. A physician reviewer classified each case identified as acute or chronic infection. Additional criteria were added to algorithms in serial fashion to improve accuracy. The best algorithm was validated by applying it to prospective electronic medical record data from June 2006 through April 2008. Completeness of case capture was assessed by comparison with state health department records.A final algorithm including a positive hepatitis B specific test, elevated transaminases and bilirubin, absence of prior positive hepatitis B tests, and absence of an ICD9 code for chronic hepatitis B identified 112/113 patients with acute hepatitis B (sensitivity 97.4%, 95% confidence interval 94-100%; specificity 93.8%, 95% confidence interval 87-100%). Application of this algorithm to prospective electronic medical record data identified 8 cases without false positives. These included 4 patients that had not been reported to the health department. There were no known cases of acute hepatitis B missed by the algorithm.An algorithm using codified electronic medical record data can reliably detect acute hepatitis B. The completeness of public health surveillance may be improved by automatically identifying notifiable diseases from electronic medical record data
IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.
Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury
Transit Timing and Duration Variations for the Discovery and Characterization of Exoplanets
Transiting exoplanets in multi-planet systems have non-Keplerian orbits which
can cause the times and durations of transits to vary. The theory and
observations of transit timing variations (TTV) and transit duration variations
(TDV) are reviewed. Since the last review, the Kepler spacecraft has detected
several hundred perturbed planets. In a few cases, these data have been used to
discover additional planets, similar to the historical discovery of Neptune in
our own Solar System. However, the more impactful aspect of TTV and TDV studies
has been characterization of planetary systems in which multiple planets
transit. After addressing the equations of motion and parameter scalings, the
main dynamical mechanisms for TTV and TDV are described, with citations to the
observational literature for real examples. We describe parameter constraints,
particularly the origin of the mass/eccentricity degeneracy and how it is
overcome by the high-frequency component of the signal. On the observational
side, derivation of timing precision and introduction to the timing diagram are
given. Science results are reviewed, with an emphasis on mass measurements of
transiting sub-Neptunes and super-Earths, from which bulk compositions may be
inferred.Comment: Revised version. Invited review submitted to 'Handbook of
Exoplanets,' Exoplanet Discovery Methods section, Springer Reference Works,
Juan Antonio Belmonte and Hans Deeg, Eds. TeX and figures may be found at
https://github.com/ericagol/TTV_revie
Transit Photometry as an Exoplanet Discovery Method
Photometry with the transit method has arguably been the most successful
exoplanet discovery method to date. A short overview about the rise of that
method to its present status is given. The method's strength is the rich set of
parameters that can be obtained from transiting planets, in particular in
combination with radial velocity observations; the basic principles of these
parameters are given. The method has however also drawbacks, which are the low
probability that transits appear in randomly oriented planet systems, and the
presence of astrophysical phenomena that may mimic transits and give rise to
false detection positives. In the second part we outline the main factors that
determine the design of transit surveys, such as the size of the survey sample,
the temporal coverage, the detection precision, the sample brightness and the
methods to extract transit events from observed light curves. Lastly, an
overview over past, current and future transit surveys is given. For these
surveys we indicate their basic instrument configuration and their planet
catch, including the ranges of planet sizes and stellar magnitudes that were
encountered. Current and future transit detection experiments concentrate
primarily on bright or special targets, and we expect that the transit method
remains a principal driver of exoplanet science, through new discoveries to be
made and through the development of new generations of instruments.Comment: Review chapte
Quantitative metric profiles capture three-dimensional temporospatial architecture to discriminate cellular functional states
<p>Abstract</p> <p>Background</p> <p>Computational analysis of tissue structure reveals sub-visual differences in tissue functional states by extracting quantitative signature features that establish a diagnostic profile. Incomplete and/or inaccurate profiles contribute to misdiagnosis.</p> <p>Methods</p> <p>In order to create more complete tissue structure profiles, we adapted our cell-graph method for extracting quantitative features from histopathology images to now capture temporospatial traits of three-dimensional collagen hydrogel cell cultures. Cell-graphs were proposed to characterize the spatial organization between the cells in tissues by exploiting graph theory wherein the nuclei of the cells constitute the <it>nodes </it>and the approximate adjacency of cells are represented with <it>edges</it>. We chose 11 different cell types representing non-tumorigenic, pre-cancerous, and malignant states from multiple tissue origins.</p> <p>Results</p> <p>We built cell-graphs from the cellular hydrogel images and computed a large set of features describing the structural characteristics captured by the graphs over time. Using three-mode tensor analysis, we identified the five most significant features (metrics) that capture the compactness, clustering, and spatial uniformity of the 3D architectural changes for each cell type throughout the time course. Importantly, four of these metrics are also the discriminative features for our histopathology data from our previous studies.</p> <p>Conclusions</p> <p>Together, these descriptive metrics provide rigorous quantitative representations of image information that other image analysis methods do not. Examining the changes in these five metrics allowed us to easily discriminate between all 11 cell types, whereas differences from visual examination of the images are not as apparent. These results demonstrate that application of the cell-graph technique to 3D image data yields discriminative metrics that have the potential to improve the accuracy of image-based tissue profiles, and thus improve the detection and diagnosis of disease.</p
The Rossiter-McLaughlin effect in Exoplanet Research
The Rossiter-McLaughlin effect occurs during a planet's transit. It provides
the main means of measuring the sky-projected spin-orbit angle between a
planet's orbital plane, and its host star's equatorial plane. Observing the
Rossiter-McLaughlin effect is now a near routine procedure. It is an important
element in the orbital characterisation of transiting exoplanets. Measurements
of the spin-orbit angle have revealed a surprising diversity, far from the
placid, Kantian and Laplacian ideals, whereby planets form, and remain, on
orbital planes coincident with their star's equator. This chapter will review a
short history of the Rossiter-McLaughlin effect, how it is modelled, and will
summarise the current state of the field before describing other uses for a
spectroscopic transit, and alternative methods of measuring the spin-orbit
angle.Comment: Review to appear as a chapter in the "Handbook of Exoplanets", ed. H.
Deeg & J.A. Belmont
Systemic hydrocortisone to prevent bronchopulmonary dysplasia in preterm infants (the SToP-BPD study); a multicenter randomized placebo controlled trial
<p>Abstract</p> <p>Background</p> <p>Randomized controlled trials have shown that treatment of chronically ventilated preterm infants after the first week of life with dexamethasone reduces the incidence of the combined outcome death or bronchopulmonary dysplasia (BPD). However, there are concerns that dexamethasone may increase the risk of adverse neurodevelopmental outcome. Hydrocortisone has been suggested as an alternative therapy. So far no randomized controlled trial has investigated its efficacy when administered after the first week of life to ventilated preterm infants.</p> <p>Methods/Design</p> <p>The SToP-BPD trial is a randomized double blind placebo controlled multicenter study including 400 very low birth weight infants (gestational age < 30 weeks and/or birth weight < 1250 grams), who are ventilator dependent at a postnatal age of 7 - 14 days. Hydrocortisone (cumulative dose 72.5 mg/kg) or placebo is administered during a 22 day tapering schedule. Primary outcome measure is the combined outcome mortality or BPD at 36 weeks postmenstrual age. Secondary outcomes are short term effects on the pulmonary condition, adverse effects during hospitalization, and long-term neurodevelopmental sequelae assessed at 2 years corrected gestational age. Analysis will be on an intention to treat basis.</p> <p>Discussion</p> <p>This trial will determine the efficacy and safety of postnatal hydrocortisone administration at a moderately early postnatal onset compared to placebo for the reduction of the combined outcome mortality and BPD at 36 weeks postmenstrual age in ventilator dependent preterm infants.</p> <p>Trial registration number</p> <p>Netherlands Trial Register (NTR): <a href="http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2768">NTR2768</a></p
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