Development of a floating tidal energy system suitable for use in shallow water

A proposal is made for the use of a traditional streamwaterwheel suspended between two floating catamaranNPL series demi-hulls as means of generating electricalpower. Two prototype devices, of lengths 1.6m and 4.5m,have been developed, constructed and tested. It was foundthat the concept is sound although greater investment isrequired with regards to the materials and bothhydrodynamic and aerodynamic design of the waterwheelto ensure an economically viable system. The workpresented concentrates on practical aspects associated withdesign, construction and trial testing in Southampton waterof the 4.5m prototype. The relatively low cost, ease ofdeployment, and the fact that conventional boat mooringsystems are effective, combine to make this an attractivealternative energy solution for remote communities

Preciseness of Subtyping on Intersection and Union Types

Abstract. The notion of subtyping has gained an important role both in theoretical and applicative domains: in lambda and concurrent calculi as well as in programming languages. The soundness and the complete-ness, together referred to as the preciseness of subtyping, can be consid-ered from two different points of view: denotational and operational. The former preciseness is based on the denotation of a type which is a math-ematical object that describes the meaning of the type in accordance with the denotations of other expressions from the language. The latter preciseness has been recently developed with respect to type safety, i.e. the safe replacement of a term of a smaller type when a term of a bigger type is expected. We propose a technique for formalising and proving operational pre-ciseness of the subtyping relation in the setting of a concurrent lambda calculus with intersection and union types. The key feature is the link between typings and the operational semantics. We then prove sound-ness and completeness getting that the subtyping relation of this calculus enjoys both denotational and operational preciseness.

Physics, Topology, Logic and Computation: A Rosetta Stone

In physics, Feynman diagrams are used to reason about quantum processes. In the 1980s, it became clear that underlying these diagrams is a powerful analogy between quantum physics and topology: namely, a linear operator behaves very much like a "cobordism". Similar diagrams can be used to reason about logic, where they represent proofs, and computation, where they represent programs. With the rise of interest in quantum cryptography and quantum computation, it became clear that there is extensive network of analogies between physics, topology, logic and computation. In this expository paper, we make some of these analogies precise using the concept of "closed symmetric monoidal category". We assume no prior knowledge of category theory, proof theory or computer science.Comment: 73 pages, 8 encapsulated postscript figure

Lamotrigine versus levetiracetam or zonisamide for focal epilepsy and valproate versus levetiracetam for generalised and unclassified epilepsy: two SANAD II non-inferiority RCTs

BackgroundLevetiracetam (Keppra®, UCB Pharma Ltd, Slough, UK) and zonisamide (Zonegran®, Eisai Co. Ltd, Tokyo, Japan) are licensed as monotherapy for focal epilepsy, and levetiracetam is increasingly used as a first-line treatment for generalised epilepsy, particularly for women of childbearing age. However, there is uncertainty as to whether or not they should be recommended as first-line treatments owing to a lack of evidence of clinical effectiveness and cost-effectiveness.ObjectivesTo compare the clinical effectiveness and cost-effectiveness of lamotrigine (Lamictal®, GlaxoSmithKline plc, Brentford, UK) (standard treatment) with levetiracetam and zonisamide (new treatments) for focal epilepsy, and to compare valproate (Epilim®, Sanofi SA, Paris, France) (standard treatment) with levetiracetam (new treatment) for generalised and unclassified epilepsy.DesignTwo pragmatic randomised unblinded non-inferiority trials run in parallel.SettingOutpatient services in NHS hospitals throughout the UK.ParticipantsThose aged ≥ 5 years with two or more spontaneous seizures that require anti-seizure medication.InterventionsParticipants with focal epilepsy were randomised to receive lamotrigine, levetiracetam or zonisamide. Participants with generalised or unclassifiable epilepsy were randomised to receive valproate or levetiracetam. The randomisation method was minimisation using a web-based program.Main outcome measuresThe primary outcome was time to 12-month remission from seizures. For this outcome, and all other time-to-event outcomes, we report hazard ratios for the standard treatment compared with the new treatment. For the focal epilepsy trial, the non-inferiority limit (lamotrigine vs. new treatments) was 1.329. For the generalised and unclassified epilepsy trial, the non-inferiority limit (valproate vs. new treatments) was 1.314. Secondary outcomes included time to treatment failure, time to first seizure, time to 24-month remission, adverse reactions, quality of life and cost-effectiveness.ResultsFocal epilepsy. A total of 990 participants were recruited, of whom 330 were randomised to receive lamotrigine, 332 were randomised to receive levetiracetam and 328 were randomised to receive zonisamide. Levetiracetam did not meet the criteria for non-inferiority (hazard ratio 1.329) in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio vs. lamotrigine 1.18, 97.5% confidence interval 0.95 to 1.47), but zonisamide did meet the criteria (hazard ratio vs. lamotrigine 1.03, 97.5% confidence interval 0.83 to 1.28). In the per-protocol analysis, lamotrigine was superior to both levetiracetam (hazard ratio 1.32, 95% confidence interval 1.05 to 1.66) and zonisamide (hazard ratio 1.37, 95% confidence interval 1.08 to 1.73). For time to treatment failure, lamotrigine was superior to levetiracetam (hazard ratio 0.60, 95% confidence interval 0.46 to 0.77) and zonisamide (hazard ratio 0.46, 95% confidence interval 0.36 to 0.60). Adverse reactions were reported by 33% of participants starting lamotrigine, 44% starting levetiracetam and 45% starting zonisamide. In the economic analysis, both levetiracetam and zonisamide were more costly and less effective than lamotrigine and were therefore dominated. Generalised and unclassifiable epilepsy. Of 520 patients recruited, 260 were randomised to receive valproate and 260 were randomised to receive to levetiracetam. A total of 397 patients had generalised epilepsy and 123 had unclassified epilepsy. Levetiracetam did not meet the criteria for non-inferiority in the primary intention-to-treat analysis of time to 12-month remission (hazard ratio 1.19, 95% confidence interval 0.96 to 1.47; non-inferiority margin 1.314). In the per-protocol analysis of time to 12-month remission, valproate was superior to levetiracetam (hazard ratio 1.68, 95% confidence interval 1.30 to 2.15). Valproate was superior to levetiracetam for time to treatment failure (hazard ratio 0.65, 95% confidence interval 0.50 to 0.83). Adverse reactions were reported by 37.4% of participants receiving valproate and 41.5% of those receiving levetiracetam. Levetiracetam was both more costly (incremental cost of £104, 95% central range -£587 to £1234) and less effective (incremental quality-adjusted life-year of -0.035, 95% central range -0.137 to 0.032) than valproate, and was therefore dominated. At a cost-effectiveness threshold of £20,000 per quality-adjusted life-year, levetiracetam was associated with a probability of 0.17 of being cost-effective.LimitationsThe SANAD II trial was unblinded, which could have biased results by influencing decisions about dosing, treatment failure and the attribution of adverse reactions.Future workSANAD II data could now be included in an individual participant meta-analysis of similar trials, and future similar trials are required to assess the clinical effectiveness and cost-effectiveness of other new treatments, including lacosamide and perampanel.ConclusionsFocal epilepsy - The SANAD II findings do not support the use of levetiracetam or zonisamide as first-line treatments in focal epilepsy. Generalised and unclassifiable epilepsy - The SANAD II findings do not support the use of levetiracetam as a first-line treatment for newly diagnosed generalised epilepsy. For women of childbearing potential, these results inform discussions about the benefit (lower teratogenicity) and harm (worse seizure outcomes and higher treatment failure rate) of levetiracetam compared with valproate.Trial registrationCurrent Controlled Trials ISRCTN30294119 and EudraCT 2012-001884-64.FundingThis project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 75. See the NIHR Journals Library website for further project information

MRI-targeted or standard biopsy for prostate-cancer diagnosis

Background Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. Methods In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. Results A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). Conclusions The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .)

Preliminary effects and acceptability of a co-produced physical activity referral intervention

Objectives: To explore the preliminary effects and acceptability of a co-produced physical activity referral intervention. Study Design: Longitudinal design with data collected at baseline and post a 12-week physical activity referral intervention. Setting. Community leisure centre. Methods: 32 adults with controlled lifestyle-related health conditions took part in a physical activity referral intervention (co-produced by a multidisciplinary stakeholder group) comprising 12 weeks’ subsidised fitness centre access plus four behaviour change consultations. A complete case analysis (t-tests and magnitude-based inferences) was conducted to assess baseline-to-12-week change in physical activity, cardiometabolic, and psychological measures. Semi-structured interviews were conducted (n=12) to explore experiences of the intervention. Results: Mean improvements were observed in cardiorespiratory fitness-2 (3.6 ml.kg.-1min-1 (95% confidence interval 1.9 to 5.4) P<0.001) and moderate-to-vigorous physical activity (12.6 min.day (95% CI 4.3 to 29.6) P=0.013). Participants were positive about the support from exercise referral practitioners, but experienced some challenges in a busy and under staffed gym environment. Conclusions: A co-produced physical activity referral intervention elicited short-term improvements in physical activity and cardiometabolic health. Further refinements may be required, via ongoing feedback between stakeholders, researchers and service users, to achieve the intended holistic physical activity focus of the intervention, prior to a definitive trial

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Atypical audiovisual speech integration in infants at risk for autism

The language difficulties often seen in individuals with autism might stem from an inability to integrate audiovisual information, a skill important for language development. We investigated whether 9-month-old siblings of older children with autism, who are at an increased risk of developing autism, are able to integrate audiovisual speech cues. We used an eye-tracker to record where infants looked when shown a screen displaying two faces of the same model, where one face is articulating/ba/and the other/ga/, with one face congruent with the syllable sound being presented simultaneously, the other face incongruent. This method was successful in showing that infants at low risk can integrate audiovisual speech: they looked for the same amount of time at the mouths in both the fusible visual/ga/− audio/ba/and the congruent visual/ba/− audio/ba/displays, indicating that the auditory and visual streams fuse into a McGurk-type of syllabic percept in the incongruent condition. It also showed that low-risk infants could perceive a mismatch between auditory and visual cues: they looked longer at the mouth in the mismatched, non-fusible visual/ba/− audio/ga/display compared with the congruent visual/ga/− audio/ga/display, demonstrating that they perceive an uncommon, and therefore interesting, speech-like percept when looking at the incongruent mouth (repeated ANOVA: displays x fusion/mismatch conditions interaction: F(1,16) = 17.153, p = 0.001). The looking behaviour of high-risk infants did not differ according to the type of display, suggesting difficulties in matching auditory and visual information (repeated ANOVA, displays x conditions interaction: F(1,25) = 0.09, p = 0.767), in contrast to low-risk infants (repeated ANOVA: displays x conditions x low/high-risk groups interaction: F(1,41) = 4.466, p = 0.041). In some cases this reduced ability might lead to the poor communication skills characteristic of autism

Untyping Typed Algebras and Colouring Cyclic Linear Logic

We prove "untyping" theorems: in some typed theories (semirings, Kleene algebras, residuated lattices, involutive residuated lattices), typed equations can be derived from the underlying untyped equations. As a consequence, the corresponding untyped decision procedures can be extended for free to the typed settings. Some of these theorems are obtained via a detour through fragments of cyclic linear logic, and give rise to a substantial optimisation of standard proof search algorithms.Comment: 21

Does it bite? The role of stimuli characteristics on preschoolers’ interactions with robots, insects and a dog

While there is increasing interest in the impact of animal interactions upon children’s wellbeing and attitudes, there has been less attention paid to the specific characteristics of the animals which attract and engage children. We used a within-subjects design to explore how differences in animal features (such as their animacy, size, and texture) impacted upon pre-school children’s social and emotional responses. This study examined pre-schoolers’ interactions with two animal-like robots (Teksta and Scoozie), two insect types (stick insects and hissing cockroaches) and a dog (Teasel, a West Highland Terrier). Nineteen preschool participants aged 35-57 months were videoed while interacting with the experimenter, a peer and each stimulus (presented individually). We used both verbal and nonverbal behaviours to evaluate interactions and emotional responses to the stimuli and found that these two measures could be incongruent, highlighting the need for systematic approaches to evaluating children’s interactions with animals. We categorised the content of children’s dialogues in relation to psychological and biological attributes of each stimulus and their distinctions between living and non-living stimuli; the majority of comments were biological, with psychological terms largely reserved for the dog and mammal-like robot only. Comments relating to living qualities revealed ambiguity towards attributes that denote differences between living and non-living creatures. We used a range of nonverbal measures, including willingness to approach and touch stimuli, rates of self-touching, facial expressions of emotion, and touch to others. Insects (hissing cockroaches and stick insects) received the most negative verbal and nonverbal responses. The mammal-like robot (rounded, fluffy body shape, large eyes, and sympathetic sounds) was viewed much more positively than its metallic counterpart, as was the real dog. We propose that these interactions provide information on how children perceive animals and a platform for the examination of human socio-emotional and cognitive development more generally. The children engaged in social referencing to the adult experimenter rather than familiar peers when uncertain about the stimuli presented, suggesting that caregivers have a primary role in shaping children’s responses to animals