Single-machine scheduling with stepwise tardiness costs and release times

We study a scheduling problem that belongs to the yard operations component of the railroad planning problems, namely the hump sequencing problem. The scheduling problem is characterized as a single-machine problem with stepwise tardiness cost objectives. This is a new scheduling criterion which is also relevant in the context of traditional machine scheduling problems. We produce complexity results that characterize some cases of the problem as pseudo-polynomially solvable. For the difficult-to-solve cases of the problem, we develop mathematical programming formulations, and propose heuristic algorithms. We test the formulations and heuristic algorithms on randomly generated single-machine scheduling problems and real-life datasets for the hump sequencing problem. Our experiments show promising results for both sets of problems

What is the easier and more reliable dose calculation for iv Phenytoin in children at risk of developing convulsive status epilepticus, 18 mg/kg or 20 mg/kg?

Background: With the Convulsive Status Guidelines due for renewal, we wondered if a phenytoin dose of ‘20 mg/kg’ would be easier to calculate correctly and therefore safer than the current ‘18 mg/kg’. An educational exercise in dose calculation was therefore undertaken to assess ease of calculation. Method: A standard question paper was prepared, comprising five clinical scenarios with children of varying ages and estimated body weights. Medical students, trainee doctors at registrar and senior house officer level, and consultant paediatricians were asked to complete the exercise, in private, by one of two medical students (SD, PS). Calculations were done with and without a calculator, for 18 mg/kg and for 20 mg/kg in randomised order. Speed and errors (greater than 10%) were determined. The data analysis was performed using SPSS version 18. Results: All answered all 20 scenarios, giving a total of 300 answers per doctor/student group, and 300 answers per type of calculation. When comparing the 2 doses, the numbers of errors more than 10% were significantly less in 20 mg/kg dose (0.33%) as compared to the 18 mg/kg dose (9.3%) (p<0.0001). Speed off calculation was significantly decreased in 20 mg/kg dose when compared with 18 mg/kg dose, with (p<0.001) or without (p<0.0001) the calculator. Speed was more than halved and errors were much less frequent by using a calculator, for the 18 mg/kg dose but no difference with or without the calculator for 20 mg/kg dose. Conclusion: We recommend that the future guidelines should suggest iv Phenytoin at 20 mg/kg rather than 18 mg/kg. This will make the calculation easier and reduce the risk of significant errors

Radiation induced angiosarcoma a sequela of radiotherapy for breast cancer following conservative surgery

Radiation induced angiosarcomas (RIA) can affect breast cancer patients who had radiotherapy following conservative breast surgery. They are very rare tumors and often their diagnosis is delayed due to their benign appearance and difficulty in differentiation from radiation induced skin changes. Therefore it is very important that clinicians are aware of their existence. We report here a case of RIA followed by discussion and review of literature

Gamma entrainment frequency affects mood, memory and cognition: an exploratory pilot study

Here we provide evidence with an exploratory pilot study that through the use of a Gamma 40 Hz entrainment frequency, mood, memory and cognition can be improved with respect to a 9-participant cohort. Participants constituted towards three binaural entrainment frequency groups: the 40 Hz, 25 Hz and 100 Hz. Participants attended a total of eight entrainment frequency sessions twice over the duration of a 4-week period. Additionally, participants were assessed based on their cognitive abilities, mood as well as memory, where the cognitive and memory assessments occurred before and after a 5-min binaural beat stimulation. The mood assessment scores were collected from sessions 1, 4 and 8, respectively. With respect to the Gamma 40 Hz entrainment frequency population, we observed a mean improvement in cognitive scores, elevating from 75% average to 85% average upon conclusion of the experimentation at weak statistical significance (α = 0.10, p = 0.076). Similarly, memory score improvements at a greater significance (α = 0.05, p = 0.0027) were noted, elevating from an average of 87% to 95%. In pertinence to the mood scores, a negative correlation across all populations were noted, inferring an overall increase in mood due to lower scores correlating with elevated mood. Finally, correlation analysis revealed a stronger R2 value (0.9838) within the 40 Hz group between sessions as well as mood score when compared across the entire frequency group cohort

The SANAD II study of the effectiveness and cost-effectiveness of levetiracetam, zonisamide, or lamotrigine for newly diagnosed focal epilepsy: an open-label, non-inferiority, multicentre, phase 4, randomised controlled trial

Background: Levetiracetam and zonisamide are licensed as monotherapy for patients with focal epilepsy, but there is uncertainty as to whether they should be recommended as first-line treatments because of insufficient evidence of clinical effectiveness and cost-effectiveness. We aimed to assess the long-term clinical effectiveness and cost-effectiveness of levetiracetam and zonisamide compared with lamotrigine in people with newly diagnosed focal epilepsy. Methods: This randomised, open-label, controlled trial compared levetiracetam and zonisamide with lamotrigine as first-line treatment for patients with newly diagnosed focal epilepsy. Adult and paediatric neurology services across the UK recruited participants aged 5 years or older (with no upper age limit) with two or more unprovoked focal seizures. Participants were randomly allocated (1:1:1) using a minimisation programme with a random element utilising factor to receive lamotrigine, levetiracetam, or zonisamide. Participants and investigators were not masked and were aware of treatment allocation. SANAD II was designed to assess non-inferiority of both levetiracetam and zonisamide to lamotrigine for the primary outcome of time to 12-month remission. Anti-seizure medications were taken orally and for participants aged 12 years or older the initial advised maintenance doses were lamotrigine 50 mg (morning) and 100 mg (evening), levetiracetam 500 mg twice per day, and zonisamide 100 mg twice per day. For children aged between 5 and 12 years the initial daily maintenance doses advised were lamotrigine 1·5 mg/kg twice per day, levetiracetam 20 mg/kg twice per day, and zonisamide 2·5 mg/kg twice per day. All participants were included in the intention-to-treat (ITT) analysis. The per-protocol (PP) analysis excluded participants with major protocol deviations and those who were subsequently diagnosed as not having epilepsy. Safety analysis included all participants who received one dose of any study drug. The non-inferiority limit was a hazard ratio (HR) of 1·329, which equates to an absolute difference of 10%. A HR greater than 1 indicated that an event was more likely on lamotrigine. The trial is registered with the ISRCTN registry, 30294119 (EudraCt number: 2012-001884-64). Findings: 990 participants were recruited between May 2, 2013, and June 20, 2017, and followed up for a further 2 years. Patients were randomly assigned to receive lamotrigine (n=330), levetiracetam (n=332), or zonisamide (n=328). The ITT analysis included all participants and the PP analysis included 324 participants randomly assigned to lamotrigine, 320 participants randomly assigned to levetiracetam, and 315 participants randomly assigned to zonisamide. Levetiracetam did not meet the criteria for non-inferiority in the ITT analysis of time to 12-month remission versus lamotrigine (HR 1·18; 97·5% CI 0·95–1·47) but zonisamide did meet the criteria for non-inferiority in the ITT analysis versus lamotrigine (1·03; 0·83–1·28). The PP analysis showed that 12-month remission was superior with lamotrigine than both levetiracetam (HR 1·32 [97·5% CI 1·05 to 1·66]) and zonisamide (HR 1·37 [1·08–1·73]). There were 37 deaths during the trial. Adverse reactions were reported by 108 (33%) participants who started lamotrigine, 144 (44%) participants who started levetiracetam, and 146 (45%) participants who started zonisamide. Lamotrigine was superior in the cost-utility analysis, with a higher net health benefit of 1·403 QALYs (97·5% central range 1·319–1·458) compared with 1·222 (1·110–1·283) for levetiracetam and 1·232 (1·112, 1·307) for zonisamide at a cost-effectiveness threshold of £20 000 per QALY. Cost-effectiveness was based on differences between treatment groups in costs and QALYs. Interpretation: These findings do not support the use of levetiracetam or zonisamide as first-line treatments for patients with focal epilepsy. Lamotrigine should remain a first-line treatment for patients with focal epilepsy and should be the standard treatment in future trials. Funding: National Institute for Health Research Health Technology Assessment programme