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"Ridgway, Tom"
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Opinion & Letters: Letter: Populism and Le Pen
Julian Barnes (French farce, G2, May 3) rightly captures the tone of fear and shame the French appear to have been feeling these last two weeks. What he doesn't say is how Le Pen's victory seems to have given some people a feeling of reassurance to speak out loud the hitherto unspeakable.
Newspaper Article
Macrophage-derived Wnt opposes Notch signaling to specify hepatic progenitor cell fate in chronic liver disease
Hepatic precursor cells (HPCs) are known to be bipotent and to give rise to both new hepatocytes and cholangiocytes upon acute liver injury. Stuart J. Forbes and his colleagues now show that interactions of HPCs with local macrophages and myofibroblasts potentiate Wnt and Notch signaling, respectively, to determine fate specification of the HPCs. Together, these mechanisms help determine proper organ regeneration after liver injury.
During chronic injury a population of bipotent hepatic progenitor cells (HPCs) become activated to regenerate both cholangiocytes and hepatocytes. Here we show in human diseased liver and mouse models of the ductular reaction that Notch and Wnt signaling direct specification of HPCs via their interactions with activated myofibroblasts or macrophages. In particular, we found that during biliary regeneration, expression of Jagged 1 (a Notch ligand) by myofibroblasts promoted Notch signaling in HPCs and thus their biliary specification to cholangiocytes. Alternatively, during hepatocyte regeneration, macrophage engulfment of hepatocyte debris induced Wnt3a expression. This resulted in canonical Wnt signaling in nearby HPCs, thus maintaining expression of Numb (a cell fate determinant) within these cells and the promotion of their specification to hepatocytes. By these two pathways adult parenchymal regeneration during chronic liver injury is promoted.
Journal Article
Body composition is associated with operative and oncologic outcomes in the management of retroperitoneal and trunk soft tissue sarcoma
Sarcopenia, myosteatosis and obesity in cancer may confer negative clinical outcomes, but their prevalence and impact among patients with retroperitoneal and trunk soft tissue sarcoma have not been systematically studied. The aim of this study was to determine body composition among patients with retroperitoneal and trunk sarcoma, and assess impact on operative and oncologic outcomes.
Consecutive patients undergoing treatment with curative intent from 2009 to 2019 were studied. Subcutaneous fat area and visceral fat areas, intramuscular adipose, lean body mass and fat mass were determined at diagnosis by CT at L3. Univariable and multivariable linear, logistic and Cox proportional hazards regression were performed.
95 patients (43.2% retroperitoneal, 48.4% trunk, 46.3% multivisceral resection) were studied. Visceral obesity was evident in 47.4%. Postoperative morbidity occurred in 25.9%, with preoperative radiotherapy (OR10.53 [95% CI 1.08–102.39], P = 0.042) and fat mass (OR1.41 [1.12–1.79], P = 0.004) independently predictive on multivariable analysis, while intramuscular adipose independently predicted inpatient LOS (P < 0.001), wound infection (P = 0.024, OR1.20 [1.02–1.40]) and major postoperative morbidity (P = 0.027, OR1.15 [1.02–1.31]). Increasing fat mass, subcutaneous fat area and intramuscular adipose were associated with greater tumor size (all P < 0.01), while intramuscular adipose predicted disease progression during neoadjuvant therapy (P = 0.024), and independently predicted disease specific survival (DSS) (P = 0.005, HR1.11 [1.03–1.20]) and overall survival (OS) on multivariable analysis (P < 0.001, HR1.19 [1.08–1.31]).
Visceral obesity is common in retroperitoneal and trunk sarcoma, and measures of adiposity are associated with adverse operative, but not oncologic outcomes. Myosteatosis is independently associated with postoperative morbidity and adverse oncologic outcomes. Body composition may represent a marker of risk among patients with retroperitoneal and trunk sarcoma.
•The impact of sarcopenia, myosteatosis and obesity on patients with soft tissue sarcoma is poorly understood.•Nutritional status is a key marker of peri-operative and oncologic risk among patients with retroperitoneal and trunk soft tissue sarcoma.•Increased adiposity was associated with postoperative morbidity, with total fat mass an independent predictor of complications.•Myosteatosis was associated with increased postoperative morbidity and adverse long-term oncologic outcomes.•Comprehensive nutritional assessment may contribute to optimization of care for patients with this complex attritional group of cancers
Journal Article
Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus — United States, May 2013–August 2016
Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan (1). Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom (2-7). To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC (8). This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.
Journal Article
Macrophage derived Wnt signalling opposes Notch signalling in a Numb mediated manner to specify HPC fate in chronic liver disease in human and mouse
During chronic injury, regeneration of the adult liver becomes impaired. In this context bipotent Hepatic Progenitor Cells (HPCs) become activated and can regenerate both cholangiocytes and hepatocytes. Notch and Wnt signalling during hepatic ontogeny are described, but their roles in HPC mediated liver regeneration are unclear. Here we show in human diseased liver and murine models of the ductular reaction with biliary and hepatocyte regeneration that Notch and Wnt signalling direct HPC specification within the activated myofibroblasts and macrophages HPC niche. During biliary regeneration, Numb is downregulated in HPCs, Jagged1 promotes biliary specification within HPCs. During hepatocyte regeneration, macrophage derived canonical Wnt signalling maintains Numb within HPCs, and Notch signalling is reduced promoting hepatocyte specification. This dominant Wnt state is stimulated through engulfment of hepatocyte debris by niche macrophages and can directly influence the HPCs. Macrophage Wnt3a expression in turn facilitates hepatocyte regeneration – thus exemplifying a novel positive feedback mechanism in adult parenchymal regeneration.
Journal Article
Disseminated Histoplasmosis in an Atlantic Bottlenose Dolphin (Tursiops truncatus)
An approximately 37-yr-old female Atlantic bottlenose dolphin (Tursiops truncatus) died after a 4-mo illness characterized by intermittent anorexia, lethargy, mild neutrophilic leukocytosis, and mild nonregenerative anemia. At necropsy, the lungs were diffusely consolidated, and histopathology of the lungs revealed severe pneumonia with macrophages containing clusters of numerous yeast cells. Inflammatory lesions and yeast also were found in pulmonary, mediastinal, prescapular, and duodenal lymph nodes, spleen, liver, kidneys, urinary bladder, pancreas, right adrenal gland, and the pyloric stomach. Histomorphology, fungal culture, and polymerase chain reaction analysis indicated that the fungus was Histoplasma capsulatum var. capsulatum. This is the first report of histoplasmosis in a cetacean.
Journal Article
Infrastructure and Strategies for Time Domain and MMA and Follow-Up
Time domain and multi-messenger astrophysics are growing and important modes of observational astronomy that will help define astrophysics in the 2020s. Significant effort is being put into developing the components of a follow-up system for dynamically turning survey alerts into data. This system consists of: 1) brokers that will aggregate, classify, and filter alerts; 2) Target Observation Managers (TOMs) for prioritizing targets and managing observations and data; and 3) observatory interfaces, schedulers, and facilities along with data reduction software and science archives. These efforts need continued community support and funding in order to complete and maintain them. Many of the efforts can be community open-source software projects but they will benefit from the leadership of professional software developers. The coordination should be done by institutions that are involved in the follow-up system such as the national observatories (e.g. LSST/Gemini/NOAO Mid-scale/Community Science and Data Center) or a new MMA institute. These tools will help the community to produce the most science from new facilities and will provide new capabilities for all users of the facilities that adopt them.
Paper
Investigation of the First Seven Reported Cases of Candida auris, a Globally Emerging Invasive, Multidrug-Resistant Fungus - United States, May 2013-August 2016
Candida auris is an emerging pathogenic fungus that has been reported from at least a dozen countries on four continents during 2009-2015. The organism is difficult to identify using traditional biochemical methods, some isolates have been found to be resistant to all three major classes of antifungal medications, and C. auris has caused health care-associated outbreaks. This is the first description of C. auris cases in the United States. C. auris appears to have emerged in the United States only in the last few years, and U.S. isolates are related to isolates from South America and South Asia. Evidence from U.S. case investigations suggests likely transmission of the organism occurred in health care settings. It is important that U.S. laboratories accurately identify C. auris and for health care facilities to implement recommended infection control practices to prevent the spread of C. auris. Local and state health departments and CDC should be notified of possible cases of C. auris and of isolates of C. haemulonii and Candida spp. that cannot be identified after routine testing.
Report