Case report: Metaplastic carcinoma presenting as a breast abscess

Metaplastic breast carcinoma (MBC) is a rare neoplasm containing a mixture of epithelial and mesenchymal elements. The epithelial component is usually ductal carcinoma but may include other variants of breast carcinomas including squamous carcinoma and osteogenic sarcoma. There is a relative paucity of data regarding such tumours. Metaplastic carcinoma carries a prognosis not dissimilar to that of comparable ductal carcinoma. This is the case of a 57 year old patient with MBC presenting with a breast abscess. A thorough literature search has not revealed any previous reports of MBC presenting as a breast abscess

Three and four dimensional computed tomographic angiography of free and pedicled flaps: investigating the vascular territories

MD (res)In plastic surgery, flap reconstruction has been utilised to repair defects in every part of the body, in an effort to restore form and function to patients. The basis of every flap is its blood supply, therefore this series of studies investigates the vascular territory of named arteries, veins and even perforators, utilizing computer tomography (CT) and TeraRecon software. The latter two is technology which allows appreciation of vascular flow in 3D and 4D (dynamic studies), whereas previous studies of vascularity has only been static and in 2D. Vascular anatomy studies were performed using fresh cadavers. Perforator flaps on the anterior trunk studied were the internal mammary artery perforator (IMAP) flap, the transverse rectus abdominis musculocutaneous (TRAM) flap, the deep inferior epigastric artery perforator (DIEP) flap and the superficial inferior epigastric artery (SIEA) flap. Posterior trunk flaps included the posterior intercostal artery perforator flap, the lumbar artery perforator flap and the superior gluteal artery perforator (SGAP) flap. In the upper extremity, we studied the supraclavicular artery perforator flap. In the lower extremity, we studied the gracilis musculocutaneous flap. Trends and characteristics are noted in the vascular analyses, and four major principles drawn are discussed in the last chapte

Assessing risk to fresh water resources from long term CO2 injection- laboratory and field studies

In developing a site for geologic sequestration, one must assess potential consequences of failure to adequately contain injected carbon dioxide (CO2). Upward migration of CO2 or displacement of saline water because of increased pressure might impact protected water resources 100s to 1000s of meters above a sequestration interval. Questions posed are: (1) Can changes in chemistry of fresh water aquifers provide evidence of CO2 leakage from deep injection/sequestration reservoirs containing brine and or hydrocarbons? (2) What parameters can we use to assess potential impacts to water quality? (3) If CO2 leakage to freshwater aquifers occurs, will groundwater quality be degraded and if so, over what time period? Modeling and reaction experiments plus known occurrences of naturally CO2-charged potable water show that the common chemical reaction products from dissolution of CO2 into freshwater include rapid buffering of acidity by dissolution of calcite and slower equilibrium by reaction with clays and feldspars. Results from a series of laboratory batch reactions of CO2 with diverse aquifer rocks show geochemical response within hours to days after introduction of CO2. Results included decreased pH and increased concentrations of cations in CO2 experimental runs relative to control runs using argon (Ar). Some cation (Ba, Ca, Fe, Mg, Mn, and Sr) concentrations increased over and an order of magnitude during CO2 runs. Results are aquifer dependant in that experimental vessels containing different aquifer rocks showed different magnitudes of increase in cation concentrations. Field studies designed to improve understanding of risk to fresh water are underway in the vicinity of (1) SACROC oilfield in Scurry County, Texas, USA where CO2 has been injected for enhanced oil recovery (EOR) since 1972 and (2) the Cranfield unit in Adams County, Mississippi, USA where CO2 EOR is currently underway. Both field studies are funded by the U.S. Department of Energy (DOE) regional carbon sequestration partnership programs and industrial sponsors. Preliminary results of groundwater monitoring are currently available for the SACROC field study where researchers investigated 68 water wells and one spring during five field excursions between June 2006 and July 2008. Results to date show no trend of preferential degradation below drinking water standards in areas of CO2 injection (inside SACROC) as compared to areas outside of the SACROC oil field.Bureau of Economic Geolog

Variation in the prices of oncology medicines across Europe and the implications for the future

Introduction/ Objectives: There are increasing concerns among health authorities regarding the sustainability of healthcare systems with growing expenditure on medicines including new high-priced oncology medicines. Medicine prices among European countries may be adversely affected by their population size and economic power to negotiate. There are also concerns that prices of patented medicines do not change once the prices of medicines used for negotiations substantially change. This needs to be investigated as part of the implications of low-cost generic oncology medicines. Methodology: Analysing principally reimbursed prices of patented oral oncology medicines (imatinib, erlotinib and fludarabine) between 2013 and 2017 across Europe and exploring correlations between GDP, population size, and prices. Comparing the findings with previous research regarding prices of oral generic oncology medicines. Results: The prices of imatinib, erlotinib and fludarabine did vary among European countries but showed limited price erosion over time in the absence of generics. There appeared to be no correlation between population size and prices. However, higher prices were seen among countries with higher GDP per capita which is a concern for lower income countries referencing these. Discussion and Conclusion: It is likely that the limited price erosion for patented oncology medicines will change across Europe with increased scrutiny over their prices and value as more medicines used for pricing decisions lose their patents combined with growing pressures on the oncology drug budget. In addition, discussions will continue regarding fair pricing for new oncology medicines and other approaches given ever rising prices with research showing substantial price reductions for oral oncology medicines (up to -97.8% for imatinib) once generics become available. We are also seeing appreciable price reductions for biosimilars further increasing the likelihood of these developments

Sixteen hundred years of increasing tree cover prior to modern deforestation in Southern Amazon and Central Brazilian savannas.

Tropical ecosystems are under increasing pressure from land-use change and deforestation. Changes in tropical forest cover are expected to affect carbon and water cycling with important implications for climatic stability at global scales. A major roadblock for predicting how tropical deforestation affects climate is the lack of baseline conditions (i.e., prior to human disturbance) of forest-savanna dynamics. To address this limitation, we developed a long-term analysis of forest and savanna distribution across the Amazon-Cerrado transition of central Brazil. We used soil organic carbon isotope ratios as a proxy for changes in woody vegetation cover over time in response to fluctuations in precipitation inferred from speleothem oxygen and strontium stable isotope records. Based on stable isotope signatures and radiocarbon activity of organic matter in soil profiles, we quantified the magnitude and direction of changes in forest and savanna ecosystem cover. Using changes in tree cover measured in 83 different locations for forests and savannas, we developed interpolation maps to assess the coherence of regional changes in vegetation. Our analysis reveals a broad pattern of woody vegetation expansion into savannas and densification within forests and savannas for at least the past ~1,600 years. The rates of vegetation change varied significantly among sampling locations possibly due to variation in local environmental factors that constrain primary productivity. The few instances in which tree cover declined (7.7% of all sampled profiles) were associated with savannas under dry conditions. Our results suggest a regional increase in moisture and expansion of woody vegetation prior to modern deforestation, which could help inform conservation and management efforts for climate change mitigation. We discuss the possible mechanisms driving forest expansion and densification of savannas directly (i.e., increasing precipitation) and indirectly (e.g., decreasing disturbance) and suggest future research directions that have the potential to improve climate and ecosystem models

Avelumab in patients with previously treated metastatic adrenocortical carcinoma: phase 1b results from the JAVELIN solid tumor trial

Abstract Background We assessed the efficacy and safety of avelumab, an anti-programmed death ligand 1 (PD-L1) antibody, in patients with previously treated metastatic adrenocortical carcinoma (mACC). Methods In this phase 1b expansion cohort, patients with mACC and prior platinum-based therapy received avelumab at 10 mg/kg intravenously every 2 weeks. Continuation of mitotane was permitted; however, mitotane levels during the study were not recorded. Tumor response was assessed by Response Evaluation Criteria In Solid Tumors v1.1. Results Fifty patients received avelumab and were followed for a median of 16.5 months. Prior treatment included ≥2 lines in 74.0%; mitotane was continued in 50.0%. The objective response rate (ORR) was 6.0% (95% CI, 1.3% to 16.5%; partial response in 3 patients). Twenty-one patients (42.0%) had stable disease as best response (disease control rate, 48.0%). Median progression-free survival was 2.6 months (95% CI, 1.4 to 4.0), median overall survival (OS) was 10.6 months (95% CI, 7.4 to 15.0), and the 1-year OS rate was 43.4% (95% CI, 27.9% to 57.9%). In evaluable patients with PD-L1+ (n = 12) or PD-L1− (n = 30) tumors (≥5% tumor cell cutoff), ORR was 16.7% vs 3.3% (P = .192). Treatment-related adverse events (TRAEs) occurred in 82.0%; the most common were nausea (20.0%), fatigue (18.0%), hypothyroidism (14.0%), and pyrexia (14.0%). Grade 3 TRAEs occurred in 16.0%; no grade 4 to 5 TRAEs occurred. Twelve patients (24.0%) had an immune-related TRAE of any grade, which were grade 3 in 2 patients (4.0%): adrenal insufficiency (n = 1), and pneumonitis (n = 1). Conclusions Avelumab showed clinical activity and a manageable safety profile in patients with platinum-treated mACC. Trial registration Clinicaltrials.gov NCT01772004; registered January 21, 2013

The subtilisin-like protease AprV2 is required for virulence and uses a novel disulphide-tethered exosite to bind substrates

Many bacterial pathogens produce extracellular proteases that degrade the extracellular matrix of the host and therefore are involved in disease pathogenesis. Dichelobacter nodosus is the causative agent of ovine footrot, a highly contagious disease that is characterized by the separation of the hoof from the underlying tissue. D. nodosus secretes three subtilisin-like proteases whose analysis forms the basis of diagnostic tests that differentiate between virulent and benign strains and have been postulated to play a role in virulence. We have constructed protease mutants of D. nodosus; their analysis in a sheep virulence model revealed that one of these enzymes, AprV2, was required for virulence. These studies challenge the previous hypothesis that the elastase activity of AprV2 is important for disease progression, since aprV2 mutants were virulent when complemented with aprB2, which encodes a variant that has impaired elastase activity. We have determined the crystal structures of both AprV2 and AprB2 and characterized the biological activity of these enzymes. These data reveal that an unusual extended disulphide-tethered loop functions as an exosite, mediating effective enzyme-substrate interactions. The disulphide bond and Tyr92, which was located at the exposed end of the loop, were functionally important. Bioinformatic analyses suggested that other pathogenic bacteria may have proteases that utilize a similar mechanism. In conclusion, we have used an integrated multidisciplinary combination of bacterial genetics, whole animal virulence trials in the original host, biochemical studies, and comprehensive analysis of crystal structures to provide the first definitive evidence that the extracellular secreted proteases produced by D. nodosus are required for virulence and to elucidate the molecular mechanism by which these proteases bind to their natural substrates. We postulate that this exosite mechanism may be used by proteases produced by other bacterial pathogens of both humans and animals