UK Cancer Healthcare Professionals Collaborating With Colleagues in Low- and Middle-Income Countries: Mapping the Extent and Nature of Partnerships; Future Implications.

AIMS: In 2020 the UK Global Cancer Network (UKGCN) was formed to unite those in the UK interested in Global Oncology and to strengthen collaborative partnerships with stakeholders working across low- and middle-income countries (LMICs) in cancer health systems, governance, and care. The UKGCN undertook a mapping exercise to document collaborations to inform the UK's global oncology strategy. MATERIALS AND METHODS: A semi-structured survey was developed and disseminated using a snowball method over ten weeks from February 2021 across the UK's cancer community, to identify individuals and institutions engaged in clinical practice, research, and/or education with partners in LMICs. The survey was sent to individuals in NHS hospitals, charities, universities, other organisations, UKGCN members, and to contacts identified by a literature and web search. RESULTS: A total of 639 invitations were sent, and 88 responses were received. Results demonstrate a range of collaborative efforts spanning many areas of cancer control: health promotion, prevention, diagnosis and treatment, survivorship, and palliative care. A wide range of countries were represented from Sub-Saharan Africa, South America, the MENA region, China, and South-East Asia. The projects included education and training (146), clinical practice/care (144), and research (226). CONCLUSION: This mapping exercise demonstrated considerable UK collaboration with stakeholders in LMICs across all three domains of education, clinical care, and research. The survey results provide an initial framework from which to promote in-depth strategic intelligence on the broad range of activities undertaken by the UK global oncology community. This information has been used as a catalyst to create new partnerships and connect colleagues working in similar geographical settings, encouraging bidirectional learning. The UKGCN will galvanise endeavours to improve equitable access to cancer services globally.

Expression of bcl-X(L) restores cell survival, but not proliferation off effector differentiation, in CD28-deficient T lymphocytes.

Lymphocytes deficient in the T cell costimulatory molecule CD28 exhibit defects in cell survival, clonal expansion, and differentiation into effector cells. It is known that CD28-mediated signaling results in the upregulation of the Bcl family member Bcl-X(L). To investigate the role that Bcl-X(L) plays in the various functions of CD28, we expressed Bcl-X(L) in CD28-deficient primary T lymphocytes using retrovirus-mediated gene transfer. T cells were activated in vitro and infected with Bcl-X(L) or control retroviruses; this method allows gene expression in activated, cycling cells. Expression of Bcl-X(L) in naive T cells was achieved by reconstitution of the immune system of lethally irradiated recipient mice with retrovirus-infected purified bone marrow stem cells from CD28(-/)- or wild-type donor mice. Our studies demonstrate that Bcl-X(L) prolongs the survival of CD28(-/)- T cells but does not restore normal proliferation or effector cell development. These results indicate that the various functions of CD28 can be dissociated, and provide an experimental approach for testing the roles of downstream signals in the functions of cellular receptors such as CD28.

Analytic system matrix resolution modeling in PET: an application to Rb-82 cardiac imaging.

This work explores application of a novel resolution modeling technique based on analytic physical models which individually models the various resolution degrading effects in PET (positron range, photon non-collinearity, inter-crystal scattering and inter-crystal penetration) followed by their combination and incorporation within the image reconstruction task. In addition to phantom studies, the proposed technique was particularly applied to and studied in the task of clinical Rb-82 myocardial perfusion imaging, which presently suffers from poor statistics and resolution properties in the reconstructed images. Overall, the approach is able to produce considerable enhancements in image quality. The reconstructed FWHM for a Discovery RX PET/CT scanner was seen to improve from 5.1 mm to 7.7 mm across the field-of-view (FoV) to approximately 3.5 mm nearly uniformly across the FoV. Furthermore, extended-source phantom studies indicated clearly improved images in terms of contrast versus noise performance. Using Monte Carlo simulations of clinical Rb-82 imaging, the resolution modeling technique was seen to significantly outperform standard reconstructions qualitatively, and also quantitatively in terms of contrast versus noise (contrast between the myocardium and other organs, as well as between myocardial defects and the left ventricle).

Resection versus no intervention or other surgical interventions for colorectal cancer liver metastases.

BACKGROUND: About one in four of patients with metastatic colorectal cancer have metastases isolated to the liver, of which 10% to 25% are eligible for ablation of the liver metastases, improving the five year survival rate. Treatments include hepatic resection and other modalities using cryosurgery and radiofrequency thermal ablation. Although new modalities allow safe ablation of liver metastases without the need for surgical intervention, there are still no clear guidelines on the appropriate management of patients with colorectal cancer and hepatic metastases. OBJECTIVES: The primary objectives were to compare resection of liver metastases to no intervention and other modalities of intervention (including cryosurgery and radiofrequency ablation) in terms of the benefits and harms for each intervention. SEARCH STRATEGY: Searches were conducted of the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE databases up to October 2006. In addition, references were scrutinized in identified eligible trials. SELECTION CRITERIA: Only randomized controlled trials reporting patients (regardless of age and sex) who had had curative surgery for adenocarcinoma of the colon or rectum, had been diagnosed with liver metastases and who were eligible for liver resection (i.e. with no evidence of primary or metastatic cancer elsewhere) were considered. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data using a form designed for this review. Discrepancies were resolved by consensus. MAIN RESULTS: Only one trial involving 123 people (87 male 36 female) was included. The data from this ten year prospective, randomized clinical trial suggest that hepatic cryosurgery is effective in the treatment of resectable and nonresectable liver metastases. The results show intra-operative tumor reduction (>/=90% or

Evaluation of meat, fruit and vegetables from retail stores in five United Kingdom regions as sources of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Escherichia coli.

We determined the prevalence and types of extended-spectrum ß-lactamase (ESBL)-producing and carbapenem-resistant Escherichia coli in raw retail beef, chicken, pork, fruit and vegetables in five UK regions in 2013-14. Raw meat (n=397), and fruit and vegetable samples (n=400) were purchased from retail stores in London, East Anglia, North West England, Scotland and Wales. Samples were tested for the presence of ESBL-producing E. coli by plating enriched samples on CHROMagar CTX and CHROMagar ESBL, for AmpC-type E. coli by plating on "CHROMagar FOX" (CHROMagar ECC+16mg/L cefoxitin), and for carbapenem-resistant E. coli by plating on CHROMagar KPC. Additionally, pre-enrichment counts were performed on the above agars, and on CHROMagar ECC. Isolates of interest were characterised by MALDI-ToF to confirm identification, by PCR for blaCIT,blaCTX-M,blaOXA, blaSHV and blaTEM genes; ESBL or blaCIT genes were sequenced. Only 1.9% and 2.5% of beef and pork samples, respectively were positive for ESBL-producing E. coli after enrichment compared with 65.4% of chicken samples. 85.6% positive samples from chicken meat carried blaCTX-M-1; blaCTX-M-15 was not detected. None of the fruits or vegetables yielded ESBL-producing E. coli and none of the meat, fruit or vegetable samples yielded carbapenem-resistant E. coli. Retail chicken was more frequently a source of ESBL-producing E. coli than were beef, pork, fruit or vegetables. None of the foodstuffs yielded E. coli with CTX-M-15 ESBL, which dominates in human clinical isolates in the UK, and none yielded carbapenem-resistant E. coli.

Cost-effectiveness of using prognostic information to select women with breast cancer for adjuvant systemic therapy.

OBJECTIVES: To investigate the cost-effectiveness of using prognostic information to identify patients with breast cancer who should receive adjuvant therapy. DATA SOURCES: Electronic databases from 1980 through to February 2002. A survey of clinical practice in UK cancer centres and units. Large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. REVIEW METHODS: Between six and nine databases were searched by an information expert. Evidence-based methods were used to review and select those studies and the quality of each included paper was assessed using standard assessment tools reported in the literature or piloted and developed for this study. A survey of clinical practice in UK cancer centres and units was carried out to ensure that conclusions drawn from the report could be implemented. These data, along with the information gathered in the systematic reviews, informed the methodological approach adopted for the health economic modelling. An illustrative framework was developed for incorporating patient-level prediction within a health economic decision model. This framework was applied to a large retrospective dataset containing data on prognostic factors, treatments and outcomes for women with early breast cancer treated in Oxford. The data were used to estimate directly a parametric regression-based risk equation, from which a prognostic index was developed, and prognosis-specific estimates of the baseline breast cancer hazard could be observed. Published estimates of treatment effects, health service treatment costs and utilities were used to construct a decision analytic framework around this risk equation, thus enabling simulation of the effectiveness and cost-effectiveness of adjuvant therapy for all possible combinations of prognostic factors included in the model. RESULTS: The lack of good-quality systematic reviews and well-conducted studies of prognostic factors in breast cancer is a striking finding. There are no registers of studies of prognostic factors or of reviews of prognostic studies. Many of the reviews used weak methods, primary studies are similar with poor methodology and reporting of results. In addition, there is much variation in patient populations, assay methods, analysis of results, definitions used and reporting of results. Most studies appear to be retrospective and some use inappropriate methods likely to inflate outcomes such as optimising cut points and failing to test the results in an independent population. Very few reviews used meta-analysis to conduct a pooled analysis and to provide an estimate of the average size of any association. Instead, most reviews relied on vote counting. Although many prognostic models for breast cancer have been published, remarkably few have been re-examined by independent groups in independent settings. The few validation studies have been carried out on ill-defined samples, sometimes of smaller size and short follow-up, and sometimes using different patient outcomes when validating a model. The evidence from the validation studies shows support for the prognostic value of the Nottingham Prognostic Index (NPI). No new prognostic factors have been shown to add substantially to those identified in the 1980s. Improvement of this index depends on finding factors that are as important as, but independent of, lymph node, stage and pathological grade. The NPI remains a useful clinical tool, although additional factors may enhance its use. We accepted that hormone receptor status (ER) for hormonal therapy such as tamoxifen and prediction of response to trastuzumab by HER2 did not require systematic review, as the mechanism of action of these drugs requires intact receptors. There was no clear evidence that other factors were useful predictors of response and survival. The survey confirmed pathological nodal status, tumour grade, tumour size and ER status as the most clinically important factors for consideration when selecting women with early breast cancer for adjuvant systemic therapy in the UK. The protocols revealed that although UK cancer centres appear to be using the same prognostic and predictive factors when selecting women to receive adjuvant therapy, much variation in clinical practice exists. Some centres use protocols based upon the NPI whereas others do not use a single index score. Within NPI and non-NPI users, between-centre variability exists in guidelines for women for whom the benefits are uncertain. Consensus amongst units appears to be greatest when selecting women for adjuvant hormone therapy with the decision based primarily upon ER or progesterone receptor status rather than combinations of a number of factors. Guidelines as to who should receive adjuvant chemotherapy, however, were found to be much less uniform. Searches of the literature revealed only five published papers that had previously examined the cost-effectiveness of using prognostic information for clinical decision-making. These studies were of varying quality and highlight the fact that economic evaluation in this area appears still to be in its infancy. By combining methodologies used in determining prognosis with those used in health economic evaluation, it was possible to illustrate an approach for simulating the effectiveness (survival and quality-adjusted survival) and the cost-effectiveness associated with the decision to treat individual women or groups of women with different prognostic characteristics. The model showed that effectiveness and cost-effectiveness of adjuvant systemic therapy have the potential to vary substantially depending upon prognosis. For some women therapy may prove very effective and cost-effective, whereas for others it may actually prove detrimental (i.e. the reductions in health-related quality of life outweigh any survival benefit). CONCLUSIONS: Outputs from the framework constructed using the methods described here have the potential to be useful for clinicians, attempting to determine whether net benefits can be obtained from administering adjuvant therapy for any presenting woman; and also for policy makers, who must be able to determine the total costs and outcomes associated with different prognosis based treatment protocols as compared with more conventional treat all or treat none policies. A risk table format enabling clinicians to look up a patient's prognostic factors to determine the likely benefits (survival and quality-adjusted survival) from administering therapy may be helpful. For policy makers, it was demonstrated that the model's output could be used to evaluate the cost-effectiveness of different treatment protocols based upon prognostic information. The framework should also be valuable in evaluating the likely impact and cost-effectiveness of new potential prognostic factors and adjuvant therapies.

Lubricity of gold nanocrystals on graphene measured using quartz crystal microbalance.

In order to test recently predicted ballistic nanofriction (ultra-low drag and enhanced lubricity) of gold nanocrystals on graphite at high surface speeds, we use the quartz microbalance technique to measure the impact of deposition of gold nanocrystals on graphene. We analyze our measurements of changes in frequency and dissipation induced by nanocrystals using a framework developed for friction of adatoms on various surfaces. We find the lubricity of gold nanocrystals on graphene to be even higher than that predicted for the ballistic nanofriction, confirming the enhanced lubricity predicted at high surface speeds. Our complementary molecular dynamics simulations indicate that such high lubricity is due to the interaction strength between gold nanocrystals and graphene being lower than previously assumed for gold nanocrystals and graphite.

Organisation of a proposed Cochrane Diet and Nutrition Field.

The Cochrane Collaboration helps people make well-informed decisions about health care by preparing, maintaining and promoting the accessibility of systematic reviews of the effects of healthcare interventions. In all, 51 Cochrane Review Groups are responsible for preparing and maintaining the reviews. Most of these Review Groups are problem-based. However, there are a number of areas or dimensions of health care, such as the setting of care (eg primary care) or the type of patient/consumer (eg older persons), that cannot be usefully conceptualised as 'health problems'. In order to reflect the interests of these dimensions, or 'fields', of health care more effectively, the Cochrane Collaboration created another type of entity: Cochrane Fields or Networks. The core functions of these Fields are described. It is proposed that a new Cochrane Subfield for Diet and Nutrition should be set up to attract a cadre of new reviewers in order to ensure the proper representation of diet and nutrition expertise in the relevant Collaborative Review Groups. The methodological pitfalls of the use of nonrandomised studies will be a key issue for the new Subfield, since the focus of the Cochrane Collaboration's programme of searching databases, journals and conference proceedings has been on the identification of reports of randomised controlled trials (RCTs). Some of these sources will be need to be searched again for non-RCT studies. The financial considerations of establishing of a Cochrane Subfield for Diet and Nutrition are discussed.

Differences in skeletal kinetics between vertebral and humeral bone measured by 18F-fluoride positron emission tomography in postmenopausal women.

We have sought to investigate regional differences in skeletal kinetics between lumbar vertebrae and the humerus of postmenopausal women with 18F-fluoride positron emission tomography (PET). Twenty-six women, mean age 62 years, had dynamic PET scans of the lumbar spine and lower humerus after the injection of 180 MBq 18F-fluoride ion. Plasma arterial input functions (IFs) were calculated from a mean IF measured arterially from 10 women and scaled according to late individual venous activity. Vertebral and humeral time activity curves were measured by placing regions of interest (ROI) over lumbar vertebrae and the humeral shaft. Using a three-compartmental model and nonlinear regression analysis the macroconstant Ki, representing plasma clearance of fluoride to bone mineral, and the individual rate constants K1 (related to regional skeletal blood flow) and k2 to k4 describing transport between plasma, an extracellular fluid compartment and a bone mineral compartment, were measured. Mean vertebral Ki (3.47x10(-2) ml x min(-1) x ml(-1)) and K1 (1.08x10(-1) ml x min(-1) x ml(-1)) were found to be significantly greater than humeral Ki (1.64x10(-2) ml min(-1) ml(-1); P<0.0001) and K1 (3.90x10(-2) ml x min(-1) x ml(-1); P<0.0001) but no significant differences were found in k2, k3, and k4. These findings confirm differences in regional skeletal kinetics between lumbar vertebrae and the lower humerus. These observations may help increase our understanding of the regional differences in pathophysiology and response to treatment that have been observed in sites consisting predominantly of either trabecular or cortical bone. 18F-fluoride PET may prove to be a valuable technique in the noninvasive measurement of regional skeletal metabolism.

Parametric images of blood flow in oncology PET studies using [15O]water.

UNLABELLED: PET was used to measure tumor blood flow, which is potentially valuable for diagnosis and assessing the effects of therapy. To help visualize regional differences in blood flow and to improve the accuracy of region-of-interest placement, a parametric imaging approach was developed and compared with the standard region-of-interest method. METHODS: Five patients with renal cell metastases in the thorax were studied using [15O]water and dynamic PET. To assess the reproducibility of the blood flow measurements, multiple water studies were performed on each patient. Model fitting was done on a pixel-by-pixel basis using several different formulations of the standard single-compartment model. RESULTS: The tumors studied spanned a wide range of blood flows, varying from 0.4 to 4.2 mL/min/g. These values were generally high compared with those of most other tissues, which meant that the tumors could be readily identified in parametric images of flow. The different model formulations produced images with different characteristics, and no model was entirely valid throughout the field of view. Although tumor blood flow measured from the parametric images was largely unbiased with respect to a standard regional method, large errors were observed with certain models in regions of low flow. The most robust model throughout the field of view had only 1 free parameter and, compared with a regional method, gave rise to a flow bias of 0.3%+/-3.1% for tumor and 16%+/-11% for low-flow soft tissue (muscle plus fat). With this model, tumor blood flow was measured with an SD of 7.6%+/-4.0%. CONCLUSION: Parametric imaging provides a convenient way of visualizing regional changes in blood flow, which may be valuable in studies of tumor blood flow.

A prototype rotating slat collimator for single photon emission computed tomography.

A collimator consisting of a series of highly attenuating parallel slats has been constructed and used in conjunction with a gamma-camera to approximately measure planar projections of a given radionuclide distribution. The enlarged solid angle of acceptance afforded by the slat collimator gave rise to an increased geometric efficiency of between 12 and 28 times that observed with a low-energy high-resolution (LEHR) parallel-hole collimator. When the slats rotated over the face of the detector and the camera gantry turned about the object, sufficient projections were acquired to reconstruct a three-dimensional (3-D) image using the inversion of the 3-D radon transform. The noise behavior of an algorithm for implementing this inversion was studied analytically and the resulting relationship has been verified by computer simulation. The substantially improved geometric efficiency of the slat collimator translated to improvements in reconstructed signal-to-noise ratio (SNR) by, at best, up to a factor of 2.0 with respect to standard parallel-hole collimation. The spatial resolution achieved with the slat collimator was comparable to that obtained with a LEHR collimator and no significant differences were observed in terms of scatter response. Accurate image quantification was hindered by the spatially variant response of the slat collimator.

Evaluation of the cognitive component of political issues by use of classical conditioning.

The direct use of verbal and physiological response measures to assess the cognitive component of a sociopolitical attitude is made difficult by the multiple meanings of sociopolitical stimuli. In the present study a modified differential classical conditioning procedure was used to produce an unambiguous physiological (skin conductance) response to stimuli related to a discrete social concept (black relatedness and not black relatedness). It was demonstrated that conditioned stimuli clearly related to this specific concept produced a conditioned response. The results also showed that a series of more ambiguous test stimuli related to the 1972-1974 election campaigns produced a gradient of skin conductance responses that was related to the degree of black relatedness or not black relatedness of each stimulus as measured by other means. The implications of the results of this study to further research and other indicators of the cognitive component of attitude are discussed.

The experimental evaluation of a prototype rotating slat collimator for planar gamma camera imaging.

A collimator consisting of a series of parallel slats has been constructed and used in conjunction with a conventional gamma camera to collect one-dimensional projections of the radioisotope distribution being imaged. With the camera remaining stationary, the collimator was made to rotate continuously over the face of the detector and the projections acquired were used to reconstruct a planar image by the theory of computed tomography. The propagation of noise on image reconstruction was largely offset by the increased geometric efficiency that resulted from the enlarged solid angle of acceptance afforded by the slat collimator. For a uniform disc of activity the signal to noise ratio (SNR) at a point in an image reconstructed by convolution and backprojection is shown to be given by [formula:see text] and Q1(xi) is the one-dimensional filter function in Fourier space. Improved noise behaviour was observed for images acquired with the slat collimator compared to those acquired with a low-energy high-resolution (LEHR) collimator for small distributions of activity. Spatial resolution with the slat collimator was approximately equal to that obtained with an LEHR collimator and improved contrast was observed in images of small hot regions.

Algorithms for calculating detector efficiency normalization coefficients for true coincidences in 3D PET.

Accurate normalization of lines of response in 3D PET is a prerequisite for quantitative reconstruction. Most current methods are component based, calculating a series of geometric and intrinsic detector efficiency factors. We have reviewed the theory behind several existing algorithms for calculating detector efficiency factors in 2D and 3D PET, and have extended them to create a range of new algorithms. Three of the algorithms described are 'fully 3D' in that they make use of data from all detector rings for the calculation of the efficiencies of any one line of response. We have assessed the performance of the new and existing methods using simulated and real data, and have demonstrated that the fully 3D algorithms allow the rapid acquisition of crystal efficiency normalization data using low-activity sources. Such methods enable the use of scatter-free scanning line sources or the use of very short acquisitions of cylindrical sources for routine normalization.

The cloverleaf skull anomaly: managing extreme cranio-orbitofaciostenosis.

The cloverleaf skull anomaly represents the most manifestly extreme form of cranio-orbitofaciostenosis with hydrocephalus that has to date been associated with a uniformly poor outcome and frequent death in infancy. Assessment of the primary deformity and the approach to treatment in a consecutive series of 10 patients with the cloverleaf skull anomaly in the one unit are presented. Early predictable surgical correction of the cranio-stenosis is possible by fronto-orbital advancement and lambdoid craniectomy. Less satisfactory correction of hydrocephalus and orbitostenosis is possible with the attendant increased morbidity. Early survival and the potential for a satisfactory long-term outcome depend on the management of the faciostenosis and an airway that may be anomalous at multiple levels. The initial approach was routine tracheostomy, which provided short-term relief but with the morbidity associated with such airway maintenance in any environment other than the most sophisticated health services. More recently, upper airway surgery (uvulopalatopharyngoplasty, adenoidectomy, and soft palatal split) has ensured airway control and avoided the progression to tracheostomy. When utilized later (1 to 10 years), such surgery may alleviate the symptoms of upper airway obstruction and sleep apnea and permit delay of midfacial advancement.

Dissemination of research findings to alcohol and other drug practitioners.

This article provides an overview of the literature in the area of research dissemination, and suggests ways of increasing communication between researchers and clinicians. It then describes a dissemination project based at the Centre for Education and Information on Drugs and Alcohol (CEIDA) which was designed to convey the results of a major research project in the alcohol and other drug area to practitioners in New South Wales. The article includes the development, implementation and evaluation of the project. The format employed-an intensive workshop conducted in different locations-was found to be a useful strategy, particularly when used to promote a large research project of clinical significance and when used in conjunction with other dissemination strategies.

A meta-analysis of the effectiveness of acupuncture in smoking cessation.

The role of acupuncture in facilitating smoking cessation is controversial. A systematic review was undertaken, incorporating meta-analytic techniques, of all the available randomized controlled trials examining the effectiveness of acupuncture in smoking cessation. Based on the data from nine trials involving 2707 patients, the odds ratio of abstinence at 6-12 months' follow-up is 1.48 (95% confidence interval 1.13-1.94) with acupuncture compared to no acupuncture or sham acupuncture. The odds of quitting were higher in comparisons between acupuncture and no acupuncture (OR 2.41, CI: 1.52 to 3.83) than between acupuncture and sham acupuncture (OR 1.16, CI: 0.90 to 1.49). Many of the included trials were small and had methodological shortcomings. Therefore, while acupuncture appears promising, there is insufficient evidence at this point, without further research, to recommend it as an effective form of therapy.

Low energy structural dynamics and constrained libration of Li(NH3)4, the lowest melting point metal.

The lattice and molecular dynamics for the solid phases of the lowest melting-point metal, Li(NH3)4, are determined by incoherent inelastic neutron scattering. Measurements of internal molecular displacements and distortions of the Li(NH3)4 units have been modelled and assigned using density functional theory calculations for the solid and molecular system. Inelastic neutron scattering measurement allow for the first determination of NH3 librational transitions.

Dark-field transmission electron microscopy and the Debye-Waller factor of graphene.

Graphene's structure bears on both the material's electronic properties and fundamental questions about long range order in two-dimensional crystals. We present an analytic calculation of selected area electron diffraction from multi-layer graphene and compare it with data from samples prepared by chemical vapor deposition and mechanical exfoliation. A single layer scatters only 0.5% of the incident electrons, so this kinematical calculation can be considered reliable for five or fewer layers. Dark-field transmission electron micrographs of multi-layer graphene illustrate how knowledge of the diffraction peak intensities can be applied for rapid mapping of thickness, stacking, and grain boundaries. The diffraction peak intensities also depend on the mean-square displacement of atoms from their ideal lattice locations, which is parameterized by a Debye-Waller factor. We measure the Debye-Waller factor of a suspended monolayer of exfoliated graphene and find a result consistent with an estimate based on the Debye model. For laboratory-scale graphene samples, finite size effects are sufficient to stabilize the graphene lattice against melting, indicating that ripples in the third dimension are not necessary.

Charged particles in radiotherapy: a 5-year update of a systematic review.

Although proton therapy has been used for many decades because of their superior dose distribution over photons and reduced integral dose, their clinical implementation is still controversial. We updated a systematic review of charged particle therapy. Although still no randomised trials were identified, the field is moving quickly and we therefore also formulated ways to move forward. In our view, the aim should be to build enough proton therapy facilities with interest in research to further improve the treatment and to run the needed clinical trials.