The photon-the quantum excitation of the electromagnetic field-is massless but carries momentum. A photon can therefore exert a force on an object upon collision
. Slowing the translational motion of ...atoms and ions by application of such a force
, known as laser cooling, was first demonstrated 40 years ago
. It revolutionized atomic physics over the following decades
, and it is now a workhorse in many fields, including studies on quantum degenerate gases, quantum information, atomic clocks and tests of fundamental physics. However, this technique has not yet been applied to antimatter. Here we demonstrate laser cooling of antihydrogen
, the antimatter atom consisting of an antiproton and a positron. By exciting the 1S-2P transition in antihydrogen with pulsed, narrow-linewidth, Lyman-α laser radiation
, we Doppler-cool a sample of magnetically trapped antihydrogen. Although we apply laser cooling in only one dimension, the trap couples the longitudinal and transverse motions of the anti-atoms, leading to cooling in all three dimensions. We observe a reduction in the median transverse energy by more than an order of magnitude-with a substantial fraction of the anti-atoms attaining submicroelectronvolt transverse kinetic energies. We also report the observation of the laser-driven 1S-2S transition in samples of laser-cooled antihydrogen atoms. The observed spectral line is approximately four times narrower than that obtained without laser cooling. The demonstration of laser cooling and its immediate application has far-reaching implications for antimatter studies. A more localized, denser and colder sample of antihydrogen will drastically improve spectroscopic
and gravitational
studies of antihydrogen in ongoing experiments. Furthermore, the demonstrated ability to manipulate the motion of antimatter atoms by laser light will potentially provide ground-breaking opportunities for future experiments, such as anti-atomic fountains, anti-atom interferometry and the creation of antimatter molecules.
Traumatic musculoskeletal injuries require advanced therapeutic intervention to heal effectively. Regenerative medicine research has aimed to address this by using biomaterials to deliver gene ...therapeutic nanoparticles (NPs) to the injury site to direct healing. However, clinical translation has proven challenging due to the short shelf-life of NPs and requirements for cold storage conditions. Thus, this study aimed to investigate lyophilisation as a process to formulate 'off-the-shelf' NPs that can be incorporated into biomaterial scaffolds at the point of use and can be stored and transported at ambient temperatures. To this end, NPs consisting of a non-viral delivery vector, glycosaminoglycan-enhanced transduction (GET) peptide, complexed with plasmid DNA (pDNA), were formulated at three charge ratios (CRs - 6, 9, 12) and lyophilised. Firstly, the effects of lyophilisation on NP physicochemical properties were investigated; it did not affect NP size, polydispersity or charge. Next, the ability of the lyophilised NPs to express the pDNA cargo in mesenchymal stem cell (MSC) 2D monolayer culture was assessed. Transfection with lyophilised NPs at each CR promoted stable transgene expression and furthermore, once lyophilised, transgene expression could be maintained following long-term storage at room temperature. Transfection with lyophilised GET-pSOX9 NPs also significantly increased MSC-mediated articular cartilage matrix deposition in methacrylated hyaluronic acid (MeHA)-collagen type II (Col II) injectable hydrogel scaffolds, highlighting the therapeutic potential of this NP formulation. In conclusion, this study outlines an effective method for formulating 'off-the-shelf' NPs for regenerative medicine applications that could be applied to the musculoskeletal system as well as other tissues.
The positron, the antiparticle of the electron, predicted by Dirac in 1931 and discovered by Anderson in 1933, plays a key role in many scientific and everyday endeavours. Notably, the positron is a ...constituent of antihydrogen, the only long-lived neutral antimatter bound state that can currently be synthesized at low energy, presenting a prominent system for testing fundamental symmetries with high precision. Here, we report on the use of laser cooled Be
ions to sympathetically cool a large and dense plasma of positrons to directly measured temperatures below 7 K in a Penning trap for antihydrogen synthesis. This will likely herald a significant increase in the amount of antihydrogen available for experimentation, thus facilitating further improvements in studies of fundamental symmetries.
Diffuse water pollution from agriculture (DWPA) is a major environmental concern, with significant adverse impacts on both human and ecosystem health. However, without an appropriate understanding of ...the multiple factors impacting on water, mitigation measures cannot be targeted. Therefore, this paper addresses this gap in understanding, reporting the hydrochemical monitoring evidence collected from the UK Government's Demonstration Test Catchments (DTC) programme including contrasting chalk and clay/mudstone catchments. We use data collected at daily and sub-daily frequency over multiple sites to address: (1) How does the behaviour of the full range of nitrogen (N) species and phosphorus (P) fractions vary? (2) How do N species and P fractions vary inter- and intra-annually? (3) What do these data indicate about the primary pollution sources? And (4) which diffuse pollution mitigation measures are appropriate in our study landscapes?
Key differences in the rates of flux of nutrients were identified, dependent on catchment characteristics. Full N speciation and P fractionation, together with dissolved organic carbon (DOC) enabled identification of the most likely contributing sources in each catchment. Nitrate (NO3-N) was the dominant N fraction in the chalk whereas organic and particulate N comprised the majority of the load in the clay/mudstone catchments. Despite current legislation, orthophosphate (PO4-P) was not found to be the dominant form of P in any of the catchments monitored. The chalk sub-catchments had the largest proportion of inorganic/dissolved organic P (DOP), accompanied by episodic delivery of particulate P (PP). Contrastingly, the clay/mudstone sub-catchments loads were dominated by PP and DOP. Thus, our results show that by monitoring both the inorganic and organic fractions a more complete picture of catchment nutrient fluxes can be determined, and sources of pollution pin-pointed. Ultimately, policy and management to bring nutrient impacts under control will only be successful if a multi-stressor approach is adopted.
Display omitted
•N speciation and P fractionation analysed for catchments with contrasting character.•Nitrate was the dominant N species in the chalk sub-catchments.•Organic and particulate N comprised the majority of the load in the clay rivers.•Orthophosphate was not found to be the dominant fraction in any of the catchments.•Particulate P was always an important P source, particularly in the clay catchments.
Purpose
Complex abdominal wall repair (CAWR) in a contaminated operative field is a challenge. Available literature regarding long-term outcomes of CAWR comprises studies that often have small ...numbers and heterogeneous patient populations. This study aims to assess long-term outcomes of modified-ventral hernia working group (VHWG) grade 3 repairs. Because the relevance of hernia recurrence (HR) as the primary outcome for this patient group is contentious, the need for further hernia surgery (FHS) was also assessed in relation to long-term survival.
Methods
A retrospective cohort study with a single prospective follow-up time-point nested in a consecutive series of patients undergoing CAWR in two European national intestinal failure centers.
Results
In long-term analysis, 266 modified VHWG grade 3 procedures were included. The overall HR rate was 32.3%. The HR rates for non-crosslinked biologic meshes and synthetic meshes when fascial closure was achieved were 20.3% and 30.6%, respectively. The rates of FHS were 7.2% and 16.7%, and occurred only within the first 3 years. Bridged repairs showed poorer results (fascial closure 22.9% hernia recurrence vs bridged 57.1% recurrence). Overall survival was relatively good with 80% en 70% of the patients still alive after 5 and 10 years, respectively. In total 86.6% of the patients remained free of FHS.
Conclusions
In this study of contaminated CAWR, non-crosslinked biologic mesh shows better results than synthetic mesh. Bridging repairs with no posterior and/or anterior fascial closure have a higher recurrence rate. The overall survival was good and the majority of patients remained free of additional hernia surgery.
Correct identification of P sources in rural watersheds is critical for the development of cost-effective measures to combat agriculturally-driven eutrophication. The chemical composition of various ...storm runoff types (field surface runoff, field drain outfalls, roads, farmyards, and septic tanks) and the receiving streams in three micro (<10 km2) watersheds of varying agricultural intensity were monitored over a 2-yr period. Mean weekly stream soluble reactive phosphorus (SRP) and total phosphorus (TP) concentrations increased from 29 and 69 μg L-1, respectively in the watershed with the lowest intensity agriculture to 382 and 503 μg L-1, respectively in the watershed with high intensity agriculture and a village sewage treatment works. Concentrations of TP in storm runoff varied by up to two orders of magnitude reflecting the complex origins, routing, and composition of contributing source areas. Application of the DESPRAL test suggested field runoff TP concentrations were influenced by both P and organic matter in soil. However, runoff from impervious surfaces (farmyard and roads), and/or influenced by septic tank discharges, was significantly more concentrated (0.08-16 mg TP L-1, mean >>1 mg L-1) than surface and subsurface runoff from cultivated land and pasture (0.02-3.6 mg TP L-1, mean <1 mg L-1), and/or contained a significantly greater proportion (>50% vs. <50%) of P in dissolved forms. It is concluded that P sources associated with the functioning of rural communities (impervious surfaces, detergents, and wastewater) may be more ecologically relevant than those associated with agriculture and should be better quantified and controlled to avoid localized eutrophication impacts.
Molecular characteristics of cancer vary between individuals. In future, most trials will require assessment of biomarkers to allocate patients into enriched populations in which targeted therapies ...are more likely to be effective. The MRC FOCUS3 trial is a feasibility study to assess key elements in the planning of such studies.
Patients with advanced colorectal cancer were registered from 24 centres between February 2010 and April 2011. With their consent, patients' tumour samples were analysed for KRAS/BRAF oncogene mutation status and topoisomerase 1 (topo-1) immunohistochemistry. Patients were then classified into one of four molecular strata; within each strata patients were randomised to one of two hypothesis-driven experimental therapies or a common control arm (FOLFIRI chemotherapy). A 4-stage suite of patient information sheets (PISs) was developed to avoid patient overload.
A total of 332 patients were registered, 244 randomised. Among randomised patients, biomarker results were provided within 10 working days (w.d.) in 71%, 15 w.d. in 91% and 20 w.d. in 99%. DNA mutation analysis was 100% concordant between two laboratories. Over 90% of participants reported excellent understanding of all aspects of the trial. In this randomised phase II setting, omission of irinotecan in the low topo-1 group was associated with increased response rate and addition of cetuximab in the KRAS, BRAF wild-type cohort was associated with longer progression-free survival.
Patient samples can be collected and analysed within workable time frames and with reproducible mutation results. Complex multi-arm designs are acceptable to patients with good PIS. Randomisation within each cohort provides outcome data that can inform clinical practice.
Background
Short-term outcomes for patients undergoing contaminated complex abdominal wall reconstruction (CCAWR), including risk stratification, have not been studied in sufficiently high numbers. ...This study aims to develop and validate risk-stratification models for Clavien–Dindo (CD) grade ≥ 3 complications in patients undergoing CCAWR.
Methods
A consecutive cohort of patients who underwent CCAWR in two European national intestinal failure centers, from January 2004 to December 2015, was identified. Data were collected retrospectively for short-term outcomes and used to develop risk models using logistic regression. A further cohort, from January 2016 to December 2017, was used to validate the models.
Results
The development cohort consisted of 272 procedures performed in 254 patients. The validation cohort consisted of 114 patients. The cohorts were comparable in baseline demographics (mean age 58.0 vs 58.1; sex 58.8% male vs 54.4%, respectively). A multi-variate model including the presence of intestinal failure (
p
< 0.01) and operative time (
p
< 0.01) demonstrated good discrimination and calibration on validation. Models for wound and intra-abdominal complications were also developed, including pre-operative immunosuppression (
p
= 0.05), intestinal failure (
p
= 0.02), increasing operative time (
p
= 0.04), increasing number of anastomoses (
p
= 0.01) and the number of previous abdominal operations (
p
= 0.02). While these models showed reasonable ability to discriminate patients on internal assessment, they were not found to be accurate on external validation.
Conclusion
Acceptable short-term outcomes after CCAWR are demonstrated. A robust model for the prediction of CD ≥ grade 3 complications has been developed and validated. This model is available online at
www.smbari.co.uk/smjconv2
.