Identifying research priorities in breast cancer surgery: a UK priority setting partnership with the James Lind Alliance.

PURPOSE: A James Lind Alliance priority setting partnership was developed to identify research priorities in breast cancer surgery from individuals with lived experience, at high genetic risk of breast cancer, and healthcare professionals (HCPs). METHODS: 'Uncertainties' were collected using an online survey. Following an evidence check and development of summary questions, an interim survey asked participants to rank their top 10 research priorities from the question list. Top-ranked questions from patient/carer, high-risk and professional groups were carried forward for discussion to a final online prioritisation workshop. RESULTS: 260 participants (101 patients/carers, 156 HCPs) submitted 940 uncertainties via the initial survey. These were analysed thematically into 128 summary questions in six topic areas. Following evidence checking, 59 questions were included in the interim survey which was completed by 572 respondents. Marked differences were seen in questions prioritised by patients/carers, HCPs and women at high-risk. The top eight priorities in patient/carer and professional groups and top two priorities for high-risk women were carried forward to the online workshop at which 22 participants discussed and agreed the final top 10. Key themes included de-escalation of breast and axillary surgery, factors impacting the development/detection of locoregional recurrence and optimal provision of support for informed treatment decision-making. CONCLUSION: The top 10 research priorities in breast cancer surgery have been agreed. However, the observed differences in research priorities identified by patients and professional groups were not anticipated. Top priorities from both groups should inform future UK breast cancer surgical research, to ensure that it addresses questions that are important to breast cancer community as a whole.

Solubility and Stability of Some Pharmaceuticals in Natural Deep Eutectic Solvents-Based Formulations.

Some medicines are poorly soluble in water. For tube feeding and parenteral administration, liquid formulations are required. The discovery of natural deep eutectic solvents (NADES) opened the way to potential applications for liquid drug formulations. NADES consists of a mixture of two or more simple natural products such as sugars, amino acids, organic acids, choline/betaine, and poly-alcohols in certain molar ratios. A series of NADES with a water content of 0-30% (w/w) was screened for the ability to solubilize (in a stable way) some poorly water-soluble pharmaceuticals at a concentration of 5 mg/mL. The results showed that NADES selectively dissolved the tested drugs. Some mixtures of choline-based NADES, acid-neutral or sugars-based NADES could dissolve chloral hydrate (dissociated in water), ranitidine·HCl (polymorphism), and methylphenidate (water insoluble), at a concentration of up to 250 mg/mL, the highest concentration tested. Whereas a mixture of lactic-acid-propyleneglycol could dissolve spironolacton and trimethoprim at a concentration up to 50 and 100 mg/mL, respectively. The results showed that NADES are promising solvents for formulation of poorly water-soluble medicines for the development of parenteral and tube feeding administration of non-water-soluble medicines. The chemical stability and bioavailability of these drug in NADES needs further studies.

A birdcage resonant antenna for helicon wave generation in TORPEX.

A birdcage resonant helicon antenna is designed, mounted, and tested in the toroidal device TORPEX. The birdcage resonant antenna is an alternative to the usual Boswell or half-helical antenna designs commonly used for ∼10 cm diameter helicon sources in low temperature plasma devices. The main advantage of the birdcage antenna lies in its resonant nature, which makes it easily operational even at large scales, an appealing feature for the TORPEX device whose poloidal cross section is 40 cm in diameter. With this antenna, helicon waves are shown to be launched and sustained throughout the whole torus of TORPEX. The helicon waves can be launched at low power on a pre-existing magnetron-generated plasma with little effect on the density profiles. The birdcage antenna can also be used alone to produce plasma, which removes the constraint of a narrow range of applied magnetic fields required by the magnetron, opening the way to a new range of studies on TORPEX with the external magnetic field as a control parameter.

Carrier surface modification for enhanced attachment and growth of anammox biofilm.

This study investigates and compares the ammonia removal kinetics, attachment, biofilm development and anammox bacteria enrichment on various surface modified carriers throughout the 163 days of start-up of an MBBR system: virgin, dextran-functionalized carriers, silica-functionalized and pre-seeded denitrifying carriers. Silica-functionalized carriers along with pre-seeded denitrifying carriers induced significant higher kinetics, faster biofilm growth and greater anammox bacteria enrichment during the 64 days of operation compared to non-modified virgin and dextran-functionalized carriers. The elevated anammox bacteria counts along with the elevated kinetics of all carriers measured at day 106 indicated that the completed biofilm growth and biofilm maturation are achieved prior to or at day 106 of start-up. The NH4+-N removal rate for virgin, dextran-functionalized, silica-functionalized and pre-seeded denitrifying carriers were achieved 0.684 ± 0.019, 0.608 ± 0.016, 0.634 ± 0.017 and 0.665 ± 0.018 g NH4+-N/m2/d, respectively, at day 106. The results demonstrate that the silica-functionalized and pre-seeded denitrifying carriers offer advantages during the early stage of start-up while the dextran-functionalized carriers did not reduce the start-up period for anammox biofilm.

Anammox attachment and biofilm development on surface-modified carriers with planktonic- and biofilm-based inoculation.

This study investigates the kinetics, attachment, biofilm development and anammox bacteria enrichment of a novel detached anammox biofilm inoculation method on non-modified virgin MBBR carriers and pre-seeded denitrifying carriers. The study compares these results to the more common use of attached anammox carriers for anammox MBBR inoculation. The anammox bacteria specific attachment-growth rates for virgin carriers inoculated with detached anammox biofilm mass were 38.1% greater for the first 25 days, leading to approximately 30% less time required to achieve complete biofilm coverage than those measured in attached biofilm carrier inoculated systems during the attachment and early biofilm growth stages. The biofilm thickness increase rate was also 52.3% higher for virgin carriers with detached biofilm inoculum. Further, inoculation using pre-seeded denitrifying carriers compared to virgin carriers demonstrated a 13.8% preferential increase in anammox bacteria specific attachment-growth rate and a corresponding 47.2% higher NH4+-N removal rate at the time of biofilm maturation.

The value of floc and biofilm bacteria for anammox stability when treating ammonia-rich digester sludge thickening lagoon supernatant.

Ammonia-rich lagoon supernatant was treated using anammox process in an integrated fixed-film activated sludge (IFAS) laboratory reactor. Effective anammox activities were demonstrated over 259 days of operation. The ammonium removal efficiency reached 94% in Phase I with influent concentrations of NH4+, NO2- and chemical oxygen demand (COD) at 250 mg-N/L, 325 mg-N/L, and 145 mg-COD/L, and reached 88% in Phase II at 420 mg-N/L, 525 mg-N/L, and 305 mg-COD/L. When supplemented with nitritation effluent for nitrite sources in Phase III, the influent COD concentration increased to 583 mg-COD/L without loss of ammonia removal efficiency (87%). The specific anammox activity was higher in biofilm than in the suspended flocs (P < 0.05), increased from Phase I to II (P < 0.05), and decreased in Phase III. Ammonia removal related genes were quantified using qPCR. Results showed higher anammox gene (AMX nirS) prevalence in biofilm, while denitrification genes (nosZ and narG) were higher in flocs (P < 0.05). Microbial community analysis showed that the seeded anammox bacteria Candidatus Brocadia was maintained at 19% in the biofilm and only 0.3% in the flocs. The major taxa in the flocs were related to denitrifiers. The floc community was affected largely under high COD conditions, but the biofilm community was not. These results suggest that the anammox activity in biofilm is resilient to high COD loadings, due to the existence of flocs with denitrification activity. The segregation of bacterial communities between biofilm and flocs in the anammox IFAS system resulted in high ammonia removal efficiency and resistance to high organic loadings.

Oxidation kinetics of cyclophosphamide and methotrexate by ozone in drinking water.

This study investigates the aqueous degradation by ozone of two target cytostatic drugs, cyclophosphamide and methotrexate. A column switching technique for on-line solid phase extraction (SPE) coupled to electro-spray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was used for the simultaneous detection of the trace contaminants. The second-order kinetic rate constants for the reaction of cyclophosphamide with molecular ozone and hydroxyl radicals were determined in bench-scale experiments at pH 8.10. The molecular ozone oxidation kinetics was studied in buffered ultrapure water and compared to the oxidation kinetics in natural water from a municipal drinking water treatment plant in the province of Quebec (Canada). For cyclophosphamide, the degradation rate constant with molecular ozone in ultrapure water was low (k(O3)=3.3+/-0.2M(-1)s(-1)) and the extent of oxidation was linearly correlated to the ozone exposure. The impact of water quality matrix on oxidation efficacy was not significant during direct ozone reaction (k(O3) =2.9+/-0.3M(-1)s(-1)). The rate constant with hydroxyl radicals was higher at 2.0 x 10(9) M(-1)s(-1). Methotrexate reacted quickly with molecular ozone at dosages typically applied in drinking water treatment (k(O3)>3.6 x 10(3)M(-1)s(-1)). Overall, the results confirmed that organic compounds reactivity with ozone was dependent of their chemical structure. Ozone was very effective against methotrexate but high oxidant concentration x contact time (CT) values were required to completely remove cyclophosphamide from drinking water. Further studies should be conducted in order to identify the ozonation by-products and explore the impact of ozone on their degradation and toxicity.