Far-from-equilibrium nanoparticle assemblies : patterns, transport and dynamics

This work is centered on the study of self-organisation and pattern formation in a prototypical nanostructured system, namely colloidal nanoparticle assemblies. The particular system chosen for investigation, Au nanocrystals spin cast onto silicon substrates from a solvent, despite being chemically rather simple exhibits a rich variety of complex patterns. In the majority of experiments discussed in this thesis, far-from-equilibrium conditions are attained by a spin-casting process which drives rapid solvent evaporation. A systematic study was carried out to determine the various factors affecting the morphology of nanoparticle assemblies produced in this manner. These factors include the concentration of the nanoparticle solution, the particular solvent used, and the chemical/ physical nature of the substrate. Changing these variables can affect both the strength of interactions between individual nanoparticles and between nanoparticles and the substrate. The various morphologies of the nanoparticle structures produced were studied using atomic force microscopy (AFM). Particular attention is paid to the role of the substrate's surface chemistry in pattern selection. A range of different substrates are used to gauge the influence of differing surface chemistries. In addition, scanning probe lithography was employed to microscopically pattern surfaces. This facilitated the observation of effects caused by the presence of two radically different surface chemistries in the micron size range. This patterning process provides the experimenter some measure of control over the morphology of the nanoparticle assembly, allowing the enforcement of predefined length scales onto the network. Simulations of drying nanocrystal films produced using code written by Martin et al [1] have been shown to accurately reproduce the experimental results. These simulations are used to develop theoretical explanations of the experimental data in terms of the varying solvent evaporation rate on the substrate and the manner by which the solvent dewets on chemically and topologically differing areas of a surface. A remarkable probe-induced coarsening of nanoparticle assemblies by repetitive scanning with an AFM probe has been studied. Repeated scanning of colloidal nanoparticle systems causes the irreversible growth of nanoparticle assemblies. The size distribution of structures produced by this growth is shown to be self-similar. With the size of the domains growing with a power law dependence on scan time. From a combination of these results the growth of structures is explained using a model of coarsening based on cluster diffusion and coalescence. This model is subtly different from coalescence in a thermally driven system due to the novel nature of the mechanical coarsening process. Electrical transport through different array morphologies produced via the spin-coating process was studied using D. C. electrical measurements and electrostatic force microscopy (EFM). Measurements over temperatures ranging from 4.5K to room temperature were made. Variations in the manner that power law scaling of the conduction behaviour alters for different arrays is linked to the topological characteristics of the arrays

Far-from-equilibrium nanoparticle assemblies : patterns, transport and dynamics

This work is centered on the study of self-organisation and pattern formation in a prototypical nanostructured system, namely colloidal nanoparticle assemblies. The particular system chosen for investigation, Au nanocrystals spin cast onto silicon substrates from a solvent, despite being chemically rather simple exhibits a rich variety of complex patterns. In the majority of experiments discussed in this thesis, far-from-equilibrium conditions are attained by a spin-casting process which drives rapid solvent evaporation. A systematic study was carried out to determine the various factors affecting the morphology of nanoparticle assemblies produced in this manner. These factors include the concentration of the nanoparticle solution, the particular solvent used, and the chemical/ physical nature of the substrate. Changing these variables can affect both the strength of interactions between individual nanoparticles and between nanoparticles and the substrate. The various morphologies of the nanoparticle structures produced were studied using atomic force microscopy (AFM). Particular attention is paid to the role of the substrate's surface chemistry in pattern selection. A range of different substrates are used to gauge the influence of differing surface chemistries. In addition, scanning probe lithography was employed to microscopically pattern surfaces. This facilitated the observation of effects caused by the presence of two radically different surface chemistries in the micron size range. This patterning process provides the experimenter some measure of control over the morphology of the nanoparticle assembly, allowing the enforcement of predefined length scales onto the network. Simulations of drying nanocrystal films produced using code written by Martin et al [1] have been shown to accurately reproduce the experimental results. These simulations are used to develop theoretical explanations of the experimental data in terms of the varying solvent evaporation rate on the substrate and the manner by which the solvent dewets on chemically and topologically differing areas of a surface. A remarkable probe-induced coarsening of nanoparticle assemblies by repetitive scanning with an AFM probe has been studied. Repeated scanning of colloidal nanoparticle systems causes the irreversible growth of nanoparticle assemblies. The size distribution of structures produced by this growth is shown to be self-similar. With the size of the domains growing with a power law dependence on scan time. From a combination of these results the growth of structures is explained using a model of coarsening based on cluster diffusion and coalescence. This model is subtly different from coalescence in a thermally driven system due to the novel nature of the mechanical coarsening process. Electrical transport through different array morphologies produced via the spin-coating process was studied using D. C. electrical measurements and electrostatic force microscopy (EFM). Measurements over temperatures ranging from 4.5K to room temperature were made. Variations in the manner that power law scaling of the conduction behaviour alters for different arrays is linked to the topological characteristics of the arrays

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

Radical surgery versus organ preservation via short-course radiotherapy followed by transanal endoscopic microsurgery for early-stage rectal cancer (TREC): a randomised, open-label feasibility study

Background: Radical surgery via total mesorectal excision might not be the optimal first-line treatment for early-stage rectal cancer. An organ-preserving strategy with selective total mesorectal excision could reduce the adverse effects of treatment without substantially compromising oncological outcomes. We investigated the feasibility of recruiting patients to a randomised trial comparing an organ-preserving strategy with total mesorectal excision. Methods: TREC was a randomised, open-label feasibility study done at 21 tertiary referral centres in the UK. Eligible participants were aged 18 years or older with rectal adenocarcinoma, staged T2 or lower, with a maximum diameter of 30 mm or less; patients with lymph node involvement or metastases were excluded. Patients were randomly allocated (1:1) by use of a computer-based randomisation service to undergo organ preservation with short-course radiotherapy followed by transanal endoscopic microsurgery after 8–10 weeks, or total mesorectal excision. Where the transanal endoscopic microsurgery specimen showed histopathological features associated with an increased risk of local recurrence, patients were considered for planned early conversion to total mesorectal excision. A non-randomised prospective registry captured patients for whom randomisation was considered inappropriate, because of a strong clinical indication for one treatment group. The primary endpoint was cumulative randomisation at 12, 18, and 24 months. Secondary outcomes evaluated safety, efficacy, and health-related quality of life assessed with the European Organisation for Research and Treatment of Cancer (EORTC) QLQ C30 and CR29 in the intention-to-treat population. This trial is registered with the ISRCTN Registry, ISRCTN14422743. Findings: Between Feb 22, 2012, and Dec 19, 2014, 55 patients were randomly assigned at 15 sites; 27 to organ preservation and 28 to radical surgery. Cumulatively, 18 patients had been randomly assigned at 12 months, 31 at 18 months, and 39 at 24 months. No patients died within 30 days of initial treatment, but one patient randomly assigned to organ preservation died within 6 months following conversion to total mesorectal excision with anastomotic leakage. Eight (30%) of 27 patients randomly assigned to organ preservation were converted to total mesorectal excision. Serious adverse events were reported in four (15%) of 27 patients randomly assigned to organ preservation versus 11 (39%) of 28 randomly assigned to total mesorectal excision (p=0·04, χ2 test). Serious adverse events associated with organ preservation were most commonly due to rectal bleeding or pain following transanal endoscopic microsurgery (reported in three cases). Radical total mesorectal excision was associated with medical and surgical complications including anastomotic leakage (two patients), kidney injury (two patients), cardiac arrest (one patient), and pneumonia (two patients). Histopathological features that would be considered to be associated with increased risk of tumour recurrence if observed after transanal endoscopic microsurgery alone were present in 16 (59%) of 27 patients randomly assigned to organ preservation, versus 24 (86%) of 28 randomly assigned to total mesorectal excision (p=0·03, χ2 test). Eight (30%) of 27 patients assigned to organ preservation achieved a complete response to radiotherapy. Patients who were randomly assigned to organ preservation showed improvements in patient-reported bowel toxicities and quality of life and function scores in multiple items compared to those who were randomly assigned to total mesorectal excision, which were sustained over 36 months’ follow-up. The non-randomised registry comprised 61 patients who underwent organ preservation and seven who underwent radical surgery. Non-randomised patients who underwent organ preservation were older than randomised patients and more likely to have life-limiting comorbidities. Serious adverse events occurred in ten (16%) of 61 non-randomised patients who underwent organ preservation versus one (14%) of seven who underwent total mesorectal excision. 24 (39%) of 61 non-randomised patients who underwent organ preservation had high-risk histopathological features, while 25 (41%) of 61 achieved a complete response. Overall, organ preservation was achieved in 19 (70%) of 27 randomised patients and 56 (92%) of 61 non-randomised patients. Interpretation: Short-course radiotherapy followed by transanal endoscopic microsurgery achieves high levels of organ preservation, with relatively low morbidity and indications of improved quality of life. These data support the use of organ preservation for patients considered unsuitable for primary total mesorectal excision due to the short-term risks associated with this surgery, and support further evaluation of short-course radiotherapy to achieve organ preservation in patients considered fit for total mesorectal excision. Larger randomised studies, such as the ongoing STAR-TREC study, are needed to more precisely determine oncological outcomes following different organ preservation treatment schedules. Funding: Cancer Research UK

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

Background: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. Methods: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. Findings: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96–1·28). Interpretation: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. Funding: National Institute for Health Research Health Services and Delivery Research Programme

Effectiveness of a national quality improvement programme to improve survival after emergency abdominal surgery (EPOCH): a stepped-wedge cluster-randomised trial

BACKGROUND: Emergency abdominal surgery is associated with poor patient outcomes. We studied the effectiveness of a national quality improvement (QI) programme to implement a care pathway to improve survival for these patients. METHODS: We did a stepped-wedge cluster-randomised trial of patients aged 40 years or older undergoing emergency open major abdominal surgery. Eligible UK National Health Service (NHS) hospitals (those that had an emergency general surgical service, a substantial volume of emergency abdominal surgery cases, and contributed data to the National Emergency Laparotomy Audit) were organised into 15 geographical clusters and commenced the QI programme in a random order, based on a computer-generated random sequence, over an 85-week period with one geographical cluster commencing the intervention every 5 weeks from the second to the 16th time period. Patients were masked to the study group, but it was not possible to mask hospital staff or investigators. The primary outcome measure was mortality within 90 days of surgery. Analyses were done on an intention-to-treat basis. This study is registered with the ISRCTN registry, number ISRCTN80682973. FINDINGS: Treatment took place between March 3, 2014, and Oct 19, 2015. 22 754 patients were assessed for elegibility. Of 15 873 eligible patients from 93 NHS hospitals, primary outcome data were analysed for 8482 patients in the usual care group and 7374 in the QI group. Eight patients in the usual care group and nine patients in the QI group were not included in the analysis because of missing primary outcome data. The primary outcome of 90-day mortality occurred in 1210 (16%) patients in the QI group compared with 1393 (16%) patients in the usual care group (HR 1·11, 0·96-1·28). INTERPRETATION: No survival benefit was observed from this QI programme to implement a care pathway for patients undergoing emergency abdominal surgery. Future QI programmes should ensure that teams have both the time and resources needed to improve patient care. FUNDING: National Institute for Health Research Health Services and Delivery Research Programme

Functionalized Surface-Confined Pores: Guest Binding Directed by Lateral Noncovalent Interactions at the Solid-Liquid Interface

We present here the construction of self-assembled two-dimensional (2D) molecular networks that contain pores equipped with functional groups that promote guest-specific binding at the liquid/solid interface. For this purpose, a dehydrobenzo[12]annulene (DBA) derivative, DBA-F, having perfluoroalkyl groups at the end of the three alternating alkoxy chains connected by para-phenylene linkers was synthesized. For comparison DBA-H, having the same carbon backbone without fluorine substituents, was also prepared. STM observations revealed that these molecules formed porous 2D networks whose pores were decorated with either fluoroalkane or simple alkane perimeters. Hexakis(phenylethynyl)benzene, HPEB, and its octadecafluoro derivative, HPEB-F surrounded by 18 fluorine atoms, were employed as planar guest molecules of suitable size. The fluoroalkane-lined pores present in the network of DBA-F exhibited good binding ability toward both guest molecules via fluorophilicity and electrostatic interaction, respectively. In contrast the binding ability of the alkane-lined pore of the network of DBA-H for the fluorinated guest HPEB-F was poor as a result of weaker electrostatic interaction. Interestingly, with HPEB as a guest, this network underwent a periodical structural deformation through an induced-fit mechanism to form a superlattice structure consisting of free and occupied pores. These observations are discussed based on modeling experiments using molecular mechanics and quantum chemical methods to elucidate the roles of lateral noncovalent interactions and size matching between the pore and the guest molecules used for 2D guest binding.status: publishe

Collective Mid-Infrared Vibrations in Surface-Enhanced Raman Scattering.

Funder: Winton Programme for the Physics of SustainabilityFunder: Cambridge Commonwealth, European and International TrustFunder: Trinity College, University of CambridgeFunder: Deutsche Akademie der Naturforscher Leopoldina - Nationale Akademie der WissenschaftenFunder: Rutherford Foundation of the Royal Society Te Aparangi of New ZealandSurface-enhanced Raman scattering (SERS) is typically assumed to occur at individual molecules neglecting intermolecular vibrational coupling. Here, we show instead how collective vibrations from infrared (IR) coupled dipoles are seen in SERS from molecular monolayers. Mixing IR-active molecules with IR-inactive spacer molecules controls the intermolecular separation. Intermolecular coupling leads to vibrational frequency upshifts up to 8 cm-1, tuning with the mixing fraction and IR dipole strength, in excellent agreement with microscopic models and density functional theory. These cooperative frequency shifts can be used as a ruler to measure intermolecular distance and disorder with angstrom resolution. We demonstrate this for photochemical reactions of 4-nitrothiophenol, which depletes the number of neighboring IR-active molecules and breaks the collective vibration, enabling direct tracking of the reaction. Collective molecular vibrations reshape SERS spectra and need to be considered in the analysis of vibrational spectra throughout analytical chemistry and sensing

Research data supporting "Collective Mid-Infrared Vibrations in Surface-Enhanced Raman Scattering"

This data set contains the experimental and simulation data for the manuscript. This includes SERS spectra and data, XPS data, and simulations. All files are given in .txt. Please see the read me file for further information how the repository is organized.We acknowledge support from the European Research Council (ERC) under Horizon 2020 research and innovation programme THOR (Grant Agreement No. 829067), PICOFORCE (Grant Agreement No. 883703) and POSEIDON (Grant Agreement No. 861950). We acknowledge funding from the EPSRC (Cambridge NanoDTC EP/L015978/1, EP/L027151/1). N.S.M. acknowledges support from the German National Academy of Sciences Leopoldina. R.A. acknowledges support from the Rutherford Foundation of the Royal Society Te Apārangi of New Zealand, the Winton Programme for the Physics of Sustainability, and Trinity College, University of Cambridge. L.A.J. acknowledges support from the Cambridge Commonwealth,European & International Trust and EPSRC award 2275079. We acknowledge use of the Cambridge XPS System, part of Sir Henry Royce Institute - Cambridge Equipment, EPSRC grant EP/P024947/1