Attosecond-Angstrom free-electron-laser towards the cold beam limit.

Electron beam quality is paramount for X-ray pulse production in free-electron-lasers (FELs). State-of-the-art linear accelerators (linacs) can deliver multi-GeV electron beams with sufficient quality for hard X-ray-FELs, albeit requiring km-scale setups, whereas plasma-based accelerators can produce multi-GeV electron beams on metre-scale distances, and begin to reach beam qualities sufficient for EUV FELs. Here we show, that electron beams from plasma photocathodes many orders of magnitude brighter than state-of-the-art can be generated in plasma wakefield accelerators (PWFAs), and then extracted, captured, transported and injected into undulators without significant quality loss. These ultrabright, sub-femtosecond electron beams can drive hard X-FELs near the cold beam limit to generate coherent X-ray pulses of attosecond-Angstrom class, reaching saturation after only 10 metres of undulator. This plasma-X-FEL opens pathways for advanced photon science capabilities, such as unperturbed observation of electronic motion inside atoms at their natural time and length scale, and towards higher photon energies.

The effect of messaging on the acceptance of swaps to reduce the energy content of snacks and non-alcoholic drinks ordered in an experimental online workplace canteen: A randomised controlled trial.

Finding effective ways to increase acceptance of lower-energy swaps offered for snacks and non-alcoholic drinks may reduce population energy intake. We examined whether incrementally increasing the tangibility of information accompanying swaps offered increased their acceptance. UK adults (n = 3481) selected a sweet snack, a savoury snack, and a drink in an experimental online canteen after being equally randomised to receive one of four messages when swaps were offered; a control message providing no specific information, a vague calorie message, an exact numeric-calories message or, a physical activity calorie equivalent (PACE). Primary outcomes were the between-group differences in (i) the odds that a sweet, savoury, or drink swap would be accepted and (ii) the energy content for each type of item ordered. Compared with control, the numeric-calories and PACE messages significantly increased the odds of accepting a sweet snack swap. All interventions significantly increased the odds of accepting savoury swaps compared with control. Only the PACE message significantly increased the odds of drink swap acceptance. The numeric-calories and PACE messages significantly reduced the energy content of sweet snacks. All interventions significantly reduced the energy content of savoury snacks. None of the intervention messages significantly reduced the energy content of drinks compared with control. Increasing the tangibility of information provided when offering swaps increased swap acceptance. PACE messaging was the most promising.

Advanced schemes for underdense plasma photocathode wakefield accelerators: pathways towards ultrahigh brightness electron beams.

The 'Trojan Horse' underdense plasma photocathode scheme applied to electron beam-driven plasma wakefield acceleration has opened up a path which promises high controllability and tunability and to reach extremely good quality as regards emittance and five-dimensional beam brightness. This combination has the potential to improve the state-of-the-art in accelerator technology significantly. In this paper, we review the basic concepts of the Trojan Horse scheme and present advanced methods for tailoring both the injector laser pulses and the witness electron bunches and combine them with the Trojan Horse scheme. These new approaches will further enhance the beam qualities, such as transverse emittance and longitudinal energy spread, and may allow, for the first time, to produce ultrahigh six-dimensional brightness electron bunches, which is a necessary requirement for driving advanced radiation sources. This article is part of the Theo Murphy meeting issue 'Directions in particle beam-driven plasma wakefield acceleration'.

Psychological stress affects the severity of radiation-induced acute skin reactions in breast cancer patients.

Psychological stress exacerbates many pathological conditions including inflammatory skin conditions. The effect of psychological stress on acute radiation-induced skin reactions has not been documented before. Here, we aimed to explore if psychological stress could aggravate skin reaction severity in breast cancer patients. We conducted a secondary analysis of patient data obtained during a randomised, controlled clinical trial for acute radiation-induced skin reaction severity in 78 breast cancer patients. Patients were assessed three times a week during treatment. Skin reaction severity was measured using the modified Radiation-Induced Skin Reaction Assessment Scale (RISRAS) and Radiation Therapy Oncology Group grades. Stress levels were determined using a 5-point LIKERT scale to rate physical well-being, managing stress levels, house, family, work and other commitments. A total of 20 patients (26%) of the 78-patient cohort were considered stressed. Skin reaction severity in stressed patients was twice that of non-stressed patients (p < 0.001) and stressed patients were five times more likely to develop moist desquamation. Our results show that psychological stress aggravates skin reaction severity during radiation therapy. This research needs to be validated in a more rigorous manner by incorporating a validated scale such as the Distress Thermometer and Impact Thermometer in future skin trials.

The Benefits of Streamlined Hip Fracture Management in a Regional Hospital.

INTRODUCTION: Hip fracture is an increasingly common injury in the growing elderly population. The morbidity and mortality associated with this injury can be reduced by minimizing delays to surgical treatment. We describe the impact of a regional hospital service redesign project that utilized the principles of smart simplicity, a management strategy that lays emphasis on collaboration to achieve desired goals. METHODS: Prior to the redesign, patients with hip fractures were taking an average of 72 hours for surgical treatment. A hip fracture working group was created to examine closely the process of hip fracture care, and a single key performance indicator (KPI) of "surgery within 48 hours" was adopted. This allowed identification of processes that could be clarified and streamlined, with the agreement of relevant stakeholders, in the creation of a new hip fracture pathway. RESULTS: In the first 3 months of the pathway's implementation, 16 of 18 patients had surgery within 48 hours of presentation. In a 6-month follow-up audit after 2 years of implementation, 36 of 39 patients were treated within 48 hours. This was significantly different to the time to surgery seen in the 12 months prior to the redesign (P < .001, Student t test). The mean time to surgery was reduced from 72 hours to 36 hours, a saving in an annual acute bed stay cost of A$152 000. DISCUSSION: Decreased time to the operating room, the cost savings inherent to this, can be achieved with the introduction of the best standard of care. A redesign that mandates collaboration in achieving a single KPI has allowed a significant culture shift in the treatment of hip fractures in our institution in the months following its institution. CONCLUSION: Collaborative, multidisciplinary collaboration has facilitated a higher standard of care and demonstrated significant cost benefit.

Reducing time to surgery after anterior cruciate ligament injury.

INTRODUCTION: Recent work suggests that reconstruction of the ruptured anterior cruciate ligament within 12 months of injury results in better outcomes. We present a complete audit cycle examining the effect of establishment of an Acute Knee Clinic on time to surgery. METHODS: Records of 20 anterior cruciate ligament reconstructions undertaken by the senior author between June 2003 and May 2004 were examined to identify the time to surgery. The Acute Knee Clinic was established in December 2004. Prospectively collected data on patients attending the Acute Knee Clinic between May 2005 and July 2007 and patients undergoing anterior cruciate ligament reconstruction from September 2006 to 2007 were reviewed with respect to referral route, time from injury to specialist review and time to surgery. RESULTS: Mean time from injury to surgery of the initial cohort was 14 months (range 3-56). After establishment of the Acute Knee Clinic, 90% of referrals from Accident and Emergency (A&E) were seen by a specialist within four weeks. Between September 2006 and September 2007, 49 patients underwent anterior cruciate ligament reconstruction: 21 came via the Acute Knee Clinic, with a mean time from injury to surgery of 6 months; 28 patients from the elective clinic had a mean time to surgery of 25 months. 95% of Acute Knee Clinic patients and 53 % of elective clinic patients had surgery within 12 months of injury. DISCUSSION: The Acute Knee Clinic has been shown to reduce the time from injury to anterior cruciate ligament reconstruction. The Acute Knee Clinic only accounts for the referral of 40% of anterior cruciate ligament reconstructions in this series: Further education work is required with A&E staff and GPs regarding the referral of knee injuries. Access to the Acute Knee Clinic could be extended to GPs, although this could create service overload.

If a trauma patient is tachycardic, should we call for a counsellor?

BACKGROUND: It has been suggested in the literature that raised heart rate in the early period after trauma is associated with the development of post-traumatic psychopathology, but little account has been taken of the potential confounding effect of injury severity. MATERIALS AND METHODS: A cohort of 154 patients, studied as part of a wider investigation of trauma outcomes, was included. Initial heart rate in the accident & emergency department, and injury severity score and new injury severity scores were recorded. Patients completed the General Health Questionnaire (GHQ-28) as a measure of psychopathology at presentation and again at two- and six-month follow-up. RESULTS: There was no relationship between psychopathology at presentation and initial heart rate or injury severity. Raised heart rate was associated with post-traumatic psychopathology at two months but not at six months. When the potential confounding effect of injury severity was controlled for, there was no independent correlation between heart rate and post-traumatic psychopathology. Injury severity score and new injury severity scores were strongly associated with GHQ-28 caseness. CONCLUSION: Post-traumatic tachycardia is not associated with development of psychopathology, but injury severity is. Previous studies that have suggested a link between tachycardia and development of psychopathology are flawed because they have not considered the confounding effect of severity of injury.

Is Anterior Cruciate Reconstruction Superior to Conservative Treatment?

Not all patients who have a rupture of the anterior cruciate ligament (ACL) elect to have surgical reconstruction. The aim of this study was to assess the short-to-medium-term results of patients who chose conservative management in comparison to patients who had reconstructive surgery within the same time period. Sixty-three patients with an ACL injury were retrospectively studied. Forty patients were managed, according to patient choice, with ACL reconstruction and 23 conservatively. Four validated questionnaires were used to assess general and knee-specific function in a cohort with a median age of 32 years and a median follow-up period of 38 months. Patients were matched on demographic variables except for gender. There were no statistically significant differences in the outcome measures, and the majority of patients would proceed with the same treatment in the event the control leg became injured. Patients who elect to have conservative management of an ACL rupture can achieve similar function and satisfaction to those who elect to have reconstruction. Until a large randomized controlled trial is conducted, patients need to be made aware of the merits of both management strategies and the lack of evidence of superiority of one over the other.

Kidney and liver transplantation in the elderly.

BACKGROUND: Transplant surgery is facing a shortage of deceased donor organs. In response, the criteria for organ donation have been extended, and an increasing number of organs from older donors are being used. For recipients, the benefits of transplantation are great, and the growing ageing population has led to increasing numbers of elderly patients being accepted for transplantation. METHODS: The literature was reviewed to investigate the impact of age of donors and recipients in abdominal organ transplantation, and to highlight aspects of the fine balance in donor and recipient selection and screening, as well as allocation policies fair to young and old alike. RESULTS: Overall, kidney and liver transplantation from older deceased donors have good outcomes, but are not as good as those from younger donors. Careful donor selection based on risk indices, and potentially biomarkers, special allocation schemes to match elderly donors with elderly recipients, and vigorous recipient selection, allows good outcomes with increasing age of both donors and recipients. The results of live kidney donation have been excellent for donor and recipient, and there is a trend towards inclusion of older donors. Future strategies, including personalized immunosuppression for older recipients as well as machine preservation and reconditioning of donor organs, are promising ways to improve the outcome of transplantation between older donors and older recipients. CONCLUSION: Kidney and liver transplantation in the elderly is a clinical reality. Outcomes are good, but can be optimized by using strategies that modify donor risk factors and recipient co-morbidities, and personalized approaches to organ allocation and immunosuppression.

The Prevalence and Severity of Joint Problems and Disability in Patients with Poliomyelitis in Urban India.

Poliomyelitis is caused by an enterovirus infection of the anterior horn cells in the spinal cord. Up to 40% of survivors recover full muscle strength, however 60-90% are left with varying degrees of residual paralysis, where the patient suffers from cramping myalgia and lower motor neuron pattern weakness. This study aimed to identify and quantify, in terms of prevalence and severity of the types of joint deformities encountered in polio sufferers. It also aimed to assess the disability caused by such problems. Finally we documented the provision and use of mobility aids, orthotics and surgery in the patient group. Impairment was confined to one lower limb, and this is consistent, as the majority of patients were infected in infancy. The study found that pes cavus, scoliosis, flexion deformity of the knee and true lower-limb shortening accounted for over half of the deformities found. The mean Barthel Disability score was 19 and over 80% of patients used at least one aid, usually in the form of a Knee-Ankle-Foot Orthosis (KAFO). Surgery also plays a large in role in the management of polio patients, however necessity needs to be assessed on an individual basis taking into account many aspects of the patient's life.

The role of hypoxia-inducible factors in organ donation and transplantation: the current perspective and future opportunities.

Hypoxia-inducible factors are the universal cellular oxygen-sensitive transcription factors that activate a number of hypoxia responsive genes, some of which are responsible for protective cellular functions. During organ donation, allografts are exposed to significant periods of hypoxia and ischemia. Exploiting this pathway during donor management and organ preservation could prevent and reduce allograft injury and improve the outcomes of organ transplantation. We review the evidence on this pathway in organ preservation, drawing on experimental studies on donor management and ischemia reperfusion injury focusing on kidney, liver, cardiac and lung transplantation. We review the major technical and experimental challenges in exploring this pathway and suggest potential future avenues for research.

Alemtuzumab and sirolimus in renal transplantation: six-year results of a single-arm prospective pilot study.

mTOR inhibitors avoid calcineurin nephrotoxicity, but sirolimus de novo is associated with unacceptable side effects and higher rejection rates. We have investigated a modified strategy: alemtuzumab induction with tacrolimus and mycophenolate maintenance, switching from tacrolimus to sirolimus at 6 months and stopping mycophenolate at 12 months. Here, we report the 6-year follow-up of 30 patients prospectively recruited to this single-arm pilot study and compare outcomes to a matched contemporaneous control group of 30 patients who received standard induction and calcineurin-inhibitor-based immunosuppression.Six-year patient and graft survival were 83% and 80%(alemtuzumab) versus 77% and 70% (control). Rejection rates in the first 6 months were similar in alemtuzumab (6.6%) and control groups (10%). A higher than expected incidence of rejection in the alemtuzumab group following cessation of mycophenolate at 1 year (17%) was mitigated in later patients by retaining low dose mycophenolate. Mean eGFR was higher in the alemtuzumab group at all time points but not significantly (p»0.16). Tacrolimus levels in the first 6 months were significantly higher in the contemporaneous control group (p<0.001). Alemtuzumab induction with initial treatment with tacrolimus enables conversion to sirolimus without the side effects and incidence of acute rejection seen in earlier protocols.

A highly emissive inorganic hexamolybdenum cluster complex as a handy precursor for the preparation of new luminescent materials.

The synthesis and characterisation of a new, highly luminescent inorganic cluster complex, (Bu4N)2[Mo6I8(NO3)6], are described. The complex possesses labile nitrato ligands and is therefore a useful precursor for the design of new luminescent materials. To exemplify this, functionalised polystyrene beads have been utilised as "polymeric ligands" to immobilise the molybdenum cluster complex.

Cognitive exposure versus avoidance in patients with chronic pain: adherence matters.

BACKGROUND: Behavioural exposure methods can reduce pain-avoidance behaviours, but outcomes vary. One possible explanation is that patients employ cognitive (experiential) avoidance during behavioural exposure. If so, reducing cognitive avoidance during behavioural exposure should help. One option is interoceptive exposure (IE), which involves sustained exposure (via attention) to pain sensations. In order to test if IE could improve outcomes from behavioural exposure, this study with mixed chronic pain patients compared outcomes from a cognitive behavioural therapy (CBT) pain management programme incorporating either IE or distraction from pain. METHODS: One hundred forty chronic pain patients were randomly assigned to CBT + IE or CBT + distraction. Outcome measures included pain, disability, depression and medication. Measures reflecting degree of threat of pain were also employed (catastrophizing, fear-avoidance, pain self-efficacy and pain acceptance). An intention-to-treat approach, using mixed-effects model repeated measures, as well as conventional inferential statistical tests, effect sizes and reliable change indices were employed to evaluate the outcomes up to 1-year post-treatment. RESULTS: Significant improvements were achieved by both treatment conditions on all outcome measures and on measures reflecting the threatening nature of pain, with no differences between treatment conditions. CONCLUSIONS: The addition of IE to behavioural exposure did not improve outcomes. However, higher adherence to either attentional strategy was associated with larger effect sizes on all measures, suggesting factors shared by the two treatments could have contributed to the outcomes. Taken as a whole, the results suggest that increasing adherence to treatment strategies, possibly by motivational measures, would improve the overall outcomes of these interventions.

Cellular uptake of ribonuclease A-functionalised core-shell silica microspheres.

Analysis of protein function in a cellular context ideally requires physiologically representative levels of that protein. Thus conventional nucleic acid-based transfection methods are far from ideal owing to the over expression that generally results. Likewise, fusions with protein transduction domains can be problematic whilst delivery via liposomes/nanoparticles typically results in endosomal localisation. Recently, polymer microspheres have been reported to be highly effective at delivering proteins into cells and thus provide a viable new alternative for protein delivery (protein transduction). Herein we describe the successful delivery of active ribonuclease A into HeLa cells via novel polymer core-silica shell microspheres. Specifically, poly(styrene-co-vinylbenzylisothiouronium chloride) core particles, generated by dispersion polymerisation, were coated with a poly(styrene-co-trimethoxysilylpropyl methacrylate) shell. The resultant core-shell morphology was characterised by transmission electron, scanning electron and confocal fluorescence microscopies, whilst size and surface charge was assessed by dynamic light scattering and zeta-potential measurements, respectively. Subsequently, ribonuclease A was coupled to the microspheres using simple carbodiimide chemistry. Gel electrophoresis confirmed and quantified the activity of the immobilised enzyme against purified HeLa RNA. Finally, the polymer-protein particles were evaluated as protein-transduction vectors in vitro to deliver active ribonuclease A to HeLa cells. Cellular uptake of the microspheres was successful and resulted in reduced levels of both intracellular RNA and cell viability.

Novel approaches to preventing ischemia-reperfusion injury during liver transplantation.

Ischemia-reperfusion injury (IRI) results in profound allograft damage during liver transplantation. The process of IRI results in adenosine triphosphatase (ATP) depletion, the production of reactive oxygen species, and progressive tissue destruction. This injury process is accelerated on reperfusion in the recipient. Over the last decade an increasing body of literature has identified a complex interplay of molecular and cellular pathways responsible for causing IRI. This article summarizes recent developments, drawing on preclinical and clinical studies, focusing on how the detrimental effects of IRI can be prevented in liver transplantation. We present a balanced overview on how machine preservation technologies, the coagulation system, antioxidants, cytoprotective agents, cytokines, preservation solutions, and the innate and adaptive immune system can be targeted to prevent IRI in liver transplantation.

The effect of body size on the rate of decomposition in a temperate region of South Africa.

Forensic anthropologists rely on the state of decomposition of a body to estimate the post-mortem-interval (PMI) which provides information about the natural events and environmental forces that could have affected the remains after death. Various factors are known to influence the rate of decomposition, among them temperature, rainfall and exposure of the body. However, conflicting reports appear in the literature on the effect of body size on the rate of decay. The aim of this project was to compare decomposition rates of large pigs (Sus scrofa; 60-90 kg), with that of small pigs (<35 kg), to assess the influence of body size on decomposition rates. For the decomposition rates of small pigs, 15 piglets were assessed three times per week over a period of three months during spring and early summer. Data collection was conducted until complete skeletonization occurred. Stages of decomposition were scored according to separate categories for each anatomical region, and the point values for each region were added to determine the total body score (TBS), which represents the overall stage of decomposition for each pig. For the large pigs, data of 15 pigs were used. Scatter plots illustrating the relationships between TBS and PMI as well as TBS and accumulated degree days (ADD) were used to assess the pattern of decomposition and to compare decomposition rates between small and large pigs. Results indicated that rapid decomposition occurs during the early stages of decomposition for both samples. Large pigs showed a plateau phase in the course of advanced stages of decomposition, during which decomposition was minimal. A similar, but much shorter plateau was reached by small pigs of >20 kg at a PMI of 20-25 days, after which decomposition commenced swiftly. This was in contrast to the small pigs of <20 kg, which showed no plateau phase and their decomposition rates were swift throughout the duration of the study. Overall, small pigs decomposed 2.82 times faster than large pigs, indicating that body size does have an effect on the rate of decomposition.

Glucocorticoid treatment does not alter early cardiac adaptations to growth restriction in preterm sheep fetuses.

OBJECTIVE: To study the consequences of glucocorticoid treatment in fetal growth restriction (FGR) on cardiac function. SETTING: Laboratory. SAMPLE: Sheep. METHODS: Growth restriction was induced in sheep fetuses using single umbilical artery ligation (SUAL) on days 105-110 of gestation (term 147). Control fetuses were not ligated. Betamethasone (BM) (11.4 mg intramuscularly) or saline was administered to ewes on days 5 and 6 after surgery. Ewes were anaesthetised on day 7, the fetuses were removed, and their hearts were mounted on a Langendorff apparatus. Balloon catheters were inserted into the right and left ventricles. OUTCOME MEASURES: Ventricular contractile function and infarct area following ischaemia/reperfusion. RESULTS: The SUAL resulted in FGR (body weight 77% of control). The FGR was associated with increases in basal left ventricular pressure development and rates of contraction and relaxation. Right ventricular contraction was unaffected. Following brief ischaemia/reperfusion, the infarct area in FGR hearts was increased four-fold compared with controls. Antenatal BM resulted in a proportional increase in heart size and coronary flow, especially in FGR fetuses, and left ventricular pressure and heart rate responses to ß-adrenoceptor activation were increased. CONCLUSIONS: Fetal hearts rapidly adapt to FGR to maintain substrate delivery to the brain and heart. The FGR greatly enhanced the area of ischaemia, with implications for susceptibility in postnatal life. Antenatal BM treatment does not interfere with these cardiac changes but appears to increase left ventricle ß-adrenoceptor responsiveness, which may render the offspring vulnerable to subsequent cardiac dysfunction.

Single bundle anterior cruciate reconstruction does not restore normal knee kinematics at six months: an upright MRI study.

Abnormal knee kinematics following reconstruction of the anterior cruciate ligament may exist despite an apparent resolution of tibial laxity and functional benefit. We performed upright, weight-bearing MR scans of both knees in the sagittal plane at different angles of flexion to determine the kinematics of the knee following unilateral reconstruction (n = 12). The uninjured knee acted as a control. Scans were performed pre-operatively and at three and six months post-operatively. Anteroposterior tibial laxity was determined using an arthrometer and patient function by validated questionnaires before and after reconstruction. In all the knees with deficient anterior cruciate ligaments, the tibial plateau was displaced anteriorly and internally rotated relative to the femur when compared with the control contralateral knee, particularly in extension and early flexion (mean lateral compartment displacement: extension 7.9 mm (sd 4.8), p = 0.002 and 30° flexion 5.1 mm (sd 3.6), p = 0.004). In all ten patients underwent post-operative scans. Reconstruction reduced the subluxation of the lateral tibial plateau at three months, with resolution of anterior displacement in early flexion, but not in extension (p = 0.015). At six months, the reconstructed knee again showed anterior subluxation in both the lateral (mean: extension 4.2 mm (sd 4.2), p = 0.021 and 30° flexion 3.2 mm (sd 3.3), p = 0.024) and medial compartments (extension, p = 0.049). Our results show that despite improvement in laxity and functional benefit, abnormal knee kinematics remain at six months and actually deteriorate from three to six months following reconstruction of the anterior cruciate ligament.

Analysis of sequential cytokine release after ACL reconstruction.

PURPOSE: Rupture of the anterior cruciate ligament is common and may necessitate surgical reconstruction. Surgical reconstruction aims to restore normal kinematics and biology within the knee. The acute phase response after surgical reconstruction remains poorly defined but may influence graft integration through modulation of host tissue remodelling. METHODS: The very early host production of key cytokines after surgery was studied. A consecutive series of 14 patients undergoing reconstructive surgery were studied per-operatively, 1 and 6 h after surgery, examining the hypothesis that the acute phase response would be non-specific but consistent between individuals, demonstrating increases of pro-inflammatory cytokines. RESULTS: A consistent increased release of monocyte-driven, non-specific, IL-1 and IL-6 release but not T cell-derived IL-2 was found. Perhaps, more interestingly, very early high concentrations of secondary growth factors PDGF and TGF-ß suggestive of an anabolic response were found. CONCLUSION: These data support the contention that an anabolic response starts earlier than previously thought within the surgically reconstructed knee.