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Mentally vulnerable defendants who struggle to effectively participate in their trial in the magistrates’ courts are not receiving the same protection as those who stand trial in the Crown Court. The Law Commission for England and Wales recognised this lacuna and suggested that the law relating to effective participation should be equally applicable in the magistrates’ courts. On closer examination of the law, the legal aid system and perspectives of legal professionals on the ‘front line’, it is clear that improvements in policy are of greater importance than legal reform and are more likely to meet the needs of these vulnerable individuals. The aim of this paper will be to demonstrate that reform of the law will be insufficient to adequately protect mentally vulnerable defendants in the magistrates’ courts and that changes in policy are needed in place of, or alongside, legal reforms.

Background The combination of nivolumab, a programmed death-1 (PD-1) targeted monoclonal antibody, with the cytotoxic T-lymphocyte antigen-4 (CTLA-4) targeted antibody, ipilimumab, represents a new standard of care in the first-line setting for patients with intermediate- and poor-risk metastatic renal cell carcinoma (mRCC) based on recent phase III data. Combining ipilimumab with nivolumab increases rates of grade 3 and 4 toxicity compared with nivolumab alone, and the optimal scheduling of these agents when used together remains unknown. The aim of the PRISM study is to assess whether less frequent dosing of ipilimumab (12-weekly versus 3-weekly), in combination with nivolumab, is associated with a favourable toxicity profile without adversely impacting efficacy. Methods The PRISM trial is a UK-based, open label, multi-centre, phase II, randomised controlled trial. The trial population consists of patients with untreated locally advanced or metastatic clear cell RCC, and aims to recruit 189 participants. Participants will be randomised on a 2:1 basis in favour of a modified schedule of 4 doses of 12-weekly ipilimumab versus a standard schedule of 4 doses of 3-weekly ipilimumab, both in combination with standard nivolumab. The proportion of participants experiencing a grade 3 or 4 adverse reaction within 12 months forms the primary endpoint of the study, but with 12-month progression free survival a key secondary endpoint. The incidence of all adverse events, discontinuation rates, overall response rate, duration of response, overall survival rates and health related quality of life will also be analysed as secondary endpoints. In addition, the potential of circulating and tissue-based biomarkers as predictors of therapy response will be explored. Discussion The combination of nivolumab with ipilimumab is active in patients with mRCC. Modifying the frequency of ipilimumab dosing may mitigate toxicity rates and positively impact quality of life without compromising efficacy, a hypothesis being explored in other tumour types such as non-small cell lung cancer. The best way to give this combination to patients with mRCC must be similarly established. Trial registration PRISM is registered with ISRCTN (reference ISRCTN95351638, 19/12/2017). Trial status At the time of submission, PRISM is open to recruitment and data collection is ongoing.

Importance: Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap. Objective: The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making. Design, Setting, and Participants: This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty. Interventions: There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m 2on day 1, capecitabine 625 mg/m 2twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care. Main Outcomes and Measures: First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival. Results: A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P =.34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes. Conclusions and Relevance: This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment. Trial Registration: isrctn.org Identifier: ISRCTN44687907.

The Law Commission published Consultation Paper No. 197 in October 2010 on unfitness to plead. This article will focus on the trial of facts hearing and the Law Commission's proposals in this regard. An examination will also be made of the Court of Appeal's judgment in R v MB given since the publication of the Law Commission Consultation Paper. The preferred route chosen by the Law Commission will be advocated, subject to concerns of properly balancing the need to protect both the vulnerable defendant from an unfair hearing and the public from the dangerous individual.

The Law Commission published Consultation Paper No. 197 in October 2010 on unfitness to plead. This article will focus on the relationship between the proposed capacity test and the abolition of the defence of doli incapax for children aged 10 or above.

The Law Commission published Consultation Paper No. 197 in October 2010 on unfitness to plead. Among the many issues to be covered were: an examination of the test for capacity which is narrower than the test for capacity under the Mental Capacity Act 2005; the scope of the trial of facts; and whether accident, mistake or self-defence could be raised as part of the defence in the context of unfitness to plead. This article will examine some of the proposals made in the Law Commission's Consultation Paper with particular focus on the meaning of capacity, along with the scope and limitations of the current law on unfitness to plead.

Gallium nitride (GaN) and related alloys are important semiconductor materials for fabricating novel photonic devices such as ultraviolet (UV) light-emitting diodes (LEDs) and vertical cavity surface-emitting lasers (VCSELs). Recent technical advances have made free-standing GaN substrates available and affordable. However, these materials are strongly resistant to wet chemical etching and also, low etch rates restrict the use of dry etching. Thus, to develop alternative high-resolution processing for these materials is increasingly important. In this paper, we report the fabrication of microstructures in free-standing GaN using pulsed UV lasers. An effective method was first developed to remove the re-deposited materials due to the laser machining. In order to achieve controllable machining and high resolution in GaN, machining parameters were carefully optimised. Under the optimised conditions, precision features such as holes (through holes, blind or tapered holes) on a tens of micrometer length scale have been machined. To fabricate micro-trenches in GaN with vertical sidewalls and a flat bottom, different process strategies of laser machining were tested and optimised. Using this technique, we have successfully fabricated high-quality micro-trenches in free-standing GaN with various widths and depths. The approach combining UV laser micromachining and other processes is also discussed. Our results demonstrate that the pulsed UV laser is a powerful tool for fabricating precision microstructures and devices in gallium nitride.

This article examines the need for a new insanity defence in the light of the inadequacies of the M'Naghten Rules. Consideration is given to some of the theoretical and practical issues which must be addressed in drafting a new insanity defence. Attention is given to American versions of the insanity defence and other proposals for reform. Tentatively, a new form of defence is suggested.

Background Over recent years a number of novel therapies have shown promise in advanced renal cell carcinoma (RCC). Internationally the standard of care of first-line therapy is sunitinib™, after a clear survival benefit was demonstrated over interferon-α. Convention dictates that sunitinib is continued until evidence of disease progression, assuming tolerability, although there is no evidence that this approach is superior to intermittent periods of treatment. The purpose of the STAR trial is to compare the standard treatment strategy (conventional continuation strategy, CCS) with a novel drug free interval strategy (DFIS) which includes planned treatment breaks. Methods/Design The STAR trial is an NIHR HTA-funded UK pragmatic randomised phase II/III clinical trial in the first-line treatment of advanced RCC. Participants will be randomised (1:1) to either a sunitinib CCS or a DFIS. The overall aim of the trial is to determine whether a DFIS is non-inferior, in terms of 2-year overall survival (OS) and quality adjusted life years (QALY) (averaged over treatment and follow up), compared to a CCS. The QALY primary endpoint was selected to assess whether any detriment in terms of OS could be balanced with improvements in quality of life (QoL). This is a complex trial with a number of design challenges, and to address these issues a feasibility stage is incorporated into the trial design. Predetermined recruitment (stage A) and efficacy (stage B) intermediary endpoints must be met to allow continuation to the overall phase III trial (stage C). An integral qualitative patient preference and understanding study will occur alongside the feasibility stage to investigate patients’ feelings regarding participation or non-participation in the trial. Discussion The optimal duration of continuing sunitinib in advanced RCC is unknown. Novel targeted therapies do not always have the same constraints to treatment duration as standard chemotherapeutic agents and currently there are no randomised data comparing different treatment durations. Incorporating planned treatment breaks has the potential to improve QoL and cost effectiveness, hopefully without significant detriment on OS, as has been demonstrated in other cancer types with other treatments. Trial Registration Controlled-trials.com ISRCTN 06473203

There is growing enthusiasm for robotic-assisted laparoscopic operations across many surgical specialities, including colorectal surgery, often not supported by robust clinical or cost-effectiveness data. A proper assessment of this new technology is required, prior to widespread recommendation or implementation.The ROLARR trial is a pan-world, prospective, randomised, controlled, unblinded, superiority trial of robotic-assisted versus standard laparoscopic surgery for the curative treatment of rectal cancer. It will investigate differences in terms of the rate of conversion to open operation, rate of pathological involvement of circumferential resection margin, 3-year local recurrence, disease-free and overall survival rates and also operative morbidity and mortality, quality of life and cost-effectiveness. The primary outcome measure is the rate of conversion to open operation. For 80% power at the 5% (two-sided) significance level, to identify a relative 50% reduction in open conversion rate (25% to 12.5%), 336 patients will be required. The target recruitment is 400 patients overall to allow loss to follow-up. Patients will be followed up at 30 days and 6 months post-operatively and then annually until 3 years after the last patient has been randomised.In many centres, robotic-assisted surgery is being implemented on the basis of theoretical advantages, which have yet to be confirmed in practice. Robotic surgery is an expensive health care provision and merits robust evaluation. The ROLARR trial is a pragmatic trial aiming to provide a comprehensive evaluation of both robotic-assisted and standard laparoscopic surgery for the curative resection of rectal cancer.

The analysis of entrapped debris provides a useful complementary method of investigating the laser ablation mechanism in laser processing of polycrystalline metal samples using a femtosecond laser (Clark MXR, CPA2001). Morphological investigations of the laser- processed areas, for a range of laser fluences and pulse number, were recorded using optical and scanning electron microscopies (SEM) and white light interferometry. Data obtained on ablation rates, ejected particle sizes, and crater morphologies prove that ablation changes from a smooth to an explosive process at high fluences, as identified with changes in the material removal mechanisms. The build-up of laser-induced mechanical stresses, due to the heating and cooling of the samples between successive laser shots, plays an important role in the material modification process, leading to the observed dependence of ablation threshold on shot number. The strength of the dependence is governed by the incubation coefficient, S, which has been measured for all materials studied. In this paper, additional insight is derived from the analysis of the debris generated for metal samples, which can be attributed to laser ablation mechanisms based on vaporization, spallation, phase explosion, and fragmentation.

The aim of the current work is two-fold: First, the aim is to investigate the transition, for a number of metals, from a smooth ablation process to an explosive one. Secondly we aim to study the dependence of the ablation threshold in metals on the applied laser shot number. Ablation of polycrystalline metal samples was performed with multiple pulses from a femtosecond laser (Clark MXR, CPA2001). Mor phological investigations of the laser processed areas were recorded using optical and scanning electron microscopies (SEM) and white light interferometry. The investigations have been carried out on sample matrices which were processed for a range of laser fluences and applied laser shots for four metals. Data obtained on ablation rates, ejected particle sizes and crater morphologies prove that ablation changes from a smooth to an explosive process at high fluences, as identified with changes in the material removal mechanisms. Threshold fluences were measured for both the smooth and explosive ablation processes. The ablation threshold fluence depends on the number of pulses applied to the same spot. It was found that the build up of laser induced mechanical stresses, due to the heating and cooling cycles of the samples between consecutive laser shots, plays an important role in the material modification process. It leads to the observed dependence of ablation threshold on shot number, which is described by a power law based on a mechanical fatigue model. The strength of the dependence is governed by the incubation coefficient, S, which has been measured for all materials studied. It is expected that the build up of laser energy or incubation leads to the accumulation of material defects and residual stresses which has the effect of lowering the energy required to cause ablation using a large number of incident laser shots. Keywords: femtosecond pulse laser, ablation threshold, material removal mechanisms, laser materials processing, metals. 1. INTRODUCTION Ultrashort pulsed laser ablation has become a very active area of research in recent years. It is definitely one of the most industrially driven technologies to have arisen from femtosecond laser applications because, through careful tailoring of the appropriate parameters, it allows practically any material to be processed with extremely high precision and with minimal collateral damage. By depositing the laser energy into the electrons of the material on a time-scale which is short compared with the transfer time of this energy to the bulk of the material, the ablation efficiency is improved and the ablation threshold is reduced and more well defined. The fundamental physical mechanisms of material removal during laser ablation are not clearly understood as yet

We present theoretical calculations and experimental measurements of silicon micromachining rates, efficiency of laser pulse utilization, and morphology changes under UV nanosecond pulses with intensities ranging from 0.5 GW/cm2 to 150 GW/cm2. Three distinct irradiance regimes are identified based on laser intensity. At low intensity, proper gas dynamics and ablation vapor plume kinetics are taken into account in our theoretical modeling. At medium high intensity, we incorporate the proper plasma dynamics, and predict the effects of the laser generated vapor plasma and the electron hole plasma on the laser-matter interaction. At even higher intensity, we attribute the observed increased ablation rate to energy re-radiation from the laser heated hot plasma, the strong shock wave, and the accompanied strong shock wave heating effects. Experimentally measured data in these regimes agree well with our calculations, without changing parameters in the calculations used for the three regimes. Our results can be applied toward quantitatively characterize the behavior of ablation results under different laser parameters to achieve optimal results for micromachining of slots and vias on silicon wafers.

The generation of debris is critical in the future application of laser technology in IC, MEMS, MOEMS manufacture. Re-deposition of debris is also critical in optimising throughput of multi-pass laser ablative processes. In this study, the debris formed in laser micromachining of wafer grade silicon is investigated. Details of the laser workstation, based on a UV DPSS laser, will be presented and the development of real time diagnostic capabilities and off-line techniques will then be described. A real time imaging capability has been used to monitor plasma and shock front propagation with nanosecond resolution. The detection system is also used to monitor spectral emission of debris and micron-sized particulate ejected from the silicon surface. Emission spectroscopy of the laser ablated silicon in the plasma show spectral features that are characteristic of atomic and molecular species on timescales of nanoseconds and microseconds, respectively, after the laser pulse. Off-line characterisation techniques have focused on investigating the distribution and chemical composition of entrapped particulate. A number of novel experimental configurations for particulate entrapment, both adjacent to and remote from the laser-ablated surface, will be described. EDX results indicate that debris generated in air is composed principally of oxygen and silicon. Additional SEM results indicate that the particulate size grows through aggregation and depends on the environment in which they are generated.

The focussed spot size of industrial laser beams is a critical processing parameter in most laser machining applications as it determines the machined feature size and the irradiance produced by the laser at the material interface. There are a number of standard methods available for accurately measuring and analysing the focussed spot. These methods often require expensive equipment that can be time consuming and difficult to set up in a production environment. This paper presents an investigation into a cost effective and straightforward method for the measurement of focussed laser spot sizes based on drilling of holes in mylar film. It can be shown that the slope of a plot of the square of the hole diameter versus the natural log of the laser pulse energy is equal to twice the square of the spot radius. A measure of the laser spot size can be calculated by generating laser-drilled holes at number of laser pulse energies. The practicality and accuracy of this method is investigated in this paper for a number of laser types including a diode pumped solid state laser (UV DPSS) operating at the third harmonic (355nm), a femtosecond laser and a flash lamp pumped Nd:YAG laser. A comparison between the measured results and the results generated with other available techniques is also presented.

821 Background: tAnGo is an ongoing 3000-patient (pt) randomized trial evaluating for the first time the role of G in adjuvant CT for breast cancer. We present the results of a preliminary prospective safety study designed to assess the incidence of any treatment (trt)-related clinical or sub-clinical disturbances of pulmonary, cardiac, or hepatic fn in the first 135 pts randomised. Methods: Pulmonary (Hb-adjusted TLCO, FEV1, FVC, CXR), cardiac (LVEF, ECG), and hepatic (AST/ALT) fn tests were conducted in 135 pts (66 EC+T, 69 EC+GT) at baseline, mid-CT, post-CT/pre-RT, and 6 months post-CT. Results: Pulmonary fn tests: majority normal at all time points, with no differences between trts or changes over time in FEV1 (p>0.3 and 0.9 resp) or FVC (p=0.95 and 0.5 resp). TLCO dropped marginally during trt (p 0.25) and no changes over time (p=0.14). Cardiac fn tests: 95% of all Echo/MUGA scans and 90% of all...

Gallium Nitride (GaN) free-standing substrate material has attracted considerable attention recently for high quality LED and Laser fabrication due to their better lattice and thermal match with the LED/Laser epi-layers than existing substrates (Sapphire or SiC). However there is still scope for the further development of both the substrate material and the epi-layer LED structures. Here we report on a preliminary investigation of the shaping capabilities of a laser-machining system on GaN LED wafer substrates. The pieces were scribed and shaped using a Nd:YVO4 diode pumped solid state AVIA 355-7000 laser (Coherent). Finally the machining of 2-dimensional scribing patterns in the free-standing wafer materials is discussed.Gallium Nitride (GaN) free-standing substrate material has attracted considerable attention recently for high quality LED and Laser fabrication due to their better lattice and thermal match with the LED/Laser epi-layers than existing substrates (Sapphire or SiC). However there is still scope for the further development of both the substrate material and the epi-layer LED structures. Here we report on a preliminary investigation of the shaping capabilities of a laser-machining system on GaN LED wafer substrates. The pieces were scribed and shaped using a Nd:YVO4 diode pumped solid state AVIA 355-7000 laser (Coherent). Finally the machining of 2-dimensional scribing patterns in the free-standing wafer materials is discussed.