Mortality, greenhouse gas emissions and consumer cost impacts of combined diet and physical activity scenarios: a health impact assessment study

$\textbf{Objective:}$ To quantify changes in mortality, greenhouse gas (GHG) emissions and consumer costs for physical activity and diet scenarios. $\textbf{Design:}$ For the physical activity scenarios, all car trips from <1 to <8 miles long were progressively replaced with cycling. For the diet scenarios, the study population was assumed to increase fruit and vegetable (F&V) consumption by 1–5 portions of F&V per day, or to eat at least 5 portions per day. Health effects were modelled with the comparative risk assessment method. Consumer costs were based on fuel cost savings and average costs of F&V, and GHG emissions to fuel usage and F&V production. $\textbf{Setting:}$ Working age population for England. $\textbf{Participants:}$ Data from the Health Survey for England, National Travel Survey and National Diet and Nutrition Survey. $\textbf{Primary outcomes measured:}$ Changes in premature deaths, consumer costs and GHG emissions stratified by age, gender and socioeconomic status (SES). $\textbf{Results:}$ Premature deaths were reduced by between 75 and 7648 cases per year for the physical activity scenarios, and 3255 and 6187 cases per year for the diet scenarios. Mortality reductions were greater among people of medium and high SES in the physical activity scenarios, whereas people with lower SES benefited more in the diet scenarios. Similarly, transport fuel costs fell more for people of high SES, whereas diet costs increased most for the lowest SES group. Net GHG emissions decreased by between 0.2 and 10.6 million tons of carbon dioxide equivalent (MtCO$_2$e) per year for the physical activity scenarios and increased by between 1.3 and 6.3 MtCO$_2$e/year for the diet scenarios. $\textbf{Conclusions:}$ Increasing F&V consumption offers the potential for large health benefits and reduces health inequalities. Replacing short car trips with cycling offers the potential for net benefits for health, GHG emissions and consumer costs.MT, PM, NJ and JW were supported by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. JW is also supported by an MRC Population Health Scientist fellowship (grant number: MR/K021796/1). CB is supported by the UK Research Councils (grant number: EPSRC EP/L024756/1) as part of the Decision Making Theme of the UK Energy Research Centre Phase 3

Sequential administration of varying doses of dacarbazine and fotemustine in advanced malignant melanoma.

There is increasing experimental evidence to suggest that expression of O6-alkylguanine-DNA-alkyltransferase (ATase) is a major factor in resistance to dacarbazine (DTIC). We recently demonstrated a progressive ATase depletion in human peripheral lymphocytes with nadir levels occurring at 4-6 h after DTIC administration (Lee et al., 1991). Therefore in an attempt to improve the clinical response rate of DTIC, fotemustine was administered 4 h after DTIC administration; since in the case of fotemustine, ATase removes the chloroethyl lesions from the O6-position of guanine, thereby preventing the formation of the cytotoxic cross-links. Sixty patients with widely metastatic melanoma received DTIC at 400, 500 or 800 mg m-2 followed by fotemustine (100 mg m-1) at 4 h after DTIC administration. Treatment was repeated every 28 days with a total of 169 cycles of chemotherapy administered; 75, 57 and 37 treatment cycles with 400, 500 and 800 mg m-2 DTIC groups respectively. Eighteen of the 60 patients responded (with three complete response); response rates were linearly related to dose, being 24%, 30% and 40% in patients receiving 400, 500 and 800 mg m-2 of DTIC respectively and the overall response rate was 30%. Median survival was 3.6 months (range, 1-15 months) with no statistically significant difference between the different DTIC treatment groups (P = 0.67). Nine patients are alive at 5 to 26 months (median 10 months); three patients with no tumour and five patients with stable disease. A statistically significant relationship was seen between the development of severe haematological toxicity (WHO > or = 3) with increasing dosage of DTIC and significant subclinical pulmonary damage was seen in 11 patients where the lung function was monitored during the course of treatment. In conclusion, it appears that with this small group of patients, escalation of DTIC dosage might not significantly affect response rates but does increase haematological toxicity. The present study provides a framework for other studies in an attempt to modulate ATase-mediated drug resistance in tumour tissues but the associated toxicity will need careful monitoring

Stacking Entropy of Hard Sphere Crystals

Classical hard spheres crystallize at equilibrium at high enough density. Crystals made up of stackings of 2-dimensional hexagonal close-packed layers (e.g. fcc, hcp, etc.) differ in entropy by only about $10^{-3}k_B$ per sphere (all configurations are degenerate in energy). To readily resolve and study these small entropy differences, we have implemented two different multicanonical Monte Carlo algorithms that allow direct equilibration between crystals with different stacking sequences. Recent work had demonstrated that the fcc stacking has higher entropy than the hcp stacking. We have studied other stackings to demonstrate that the fcc stacking does indeed have the highest entropy of ALL possible stackings. The entropic interactions we could detect involve three, four and (although with less statistical certainty) five consecutive layers of spheres. These interlayer entropic interactions fall off in strength with increasing distance, as expected; this fall-off appears to be much slower near the melting density than at the maximum (close-packing) density. At maximum density the entropy difference between fcc and hcp stackings is $0.00115 +/- 0.00004 k_B$ per sphere, which is roughly 30% higher than the same quantity measured near the melting transition.Comment: 15 page

Obtaining patient torso geometry for the design of scoliosis braces. A study of the accuracy and repeatability of handheld 3D scanners

Objective: Obtaining patient geometry is crucial in scoliosis brace design for patients with adolescent idiopathic scoliosis. Advances in 3D scanning technologies provide the opportunity to obtain patient geometries quickly with fewer resources during the design process compared with the plaster-cast method. This study assesses the accuracy and repeatability of such technologies for this application. Methods: The accuracy and repeatability of three different handheld scanners and phone-photogrammetry was assessed using different mesh generation software. Twenty-four scans of a single subject's torso were analyzed for accuracy and repeatability based on anatomical landmark distances and surface deviation maps. Results: Mark II and Structure ST01 scanners showed maximum mean surface deviations of 1.74 ± 3.63 mm and 1.64 ± 3.06 mm, respectively. Deviations were lower for the Peel 1 scanner (maximum of −0.35 ± 2.8 mm) but higher with the use of phone-photogrammetry (maximum of −5.1 ± 4.8 mm). The mean absolute errors of anatomical landmark distance measurements from torso meshes obtained with the Peel 1, Mark II, and ST01 scanners were all within 9.3 mm (3.6%), whereas phone-photogrammetry errors were as high as 18 mm (7%). Conclusions: Low-cost Mark II and ST01 scanners are recommended for obtaining torso geometries because of their accuracy and repeatability. Subject’s breathing/movement affects the resultant geometry around the abdominal and anterolateral regions

Systematic review and meta-analysis of reduction in all-cause mortality from walking and cycling and shape of dose response relationship

BACKGROUND AND OBJECTIVE: Walking and cycling have shown beneficial effects on population risk of all-cause mortality (ACM). This paper aims to review the evidence and quantify these effects, adjusted for other physical activity (PA). DATA SOURCES: We conducted a systematic review to identify relevant studies. Searches were conducted in November 2013 using the following health databases of publications: Embase (OvidSP); Medline (OvidSP); Web of Knowledge; CINAHL; SCOPUS; SPORTDiscus. We also searched reference lists of relevant texts and reviews. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: Eligible studies were prospective cohort design and reporting walking or cycling exposure and mortality as an outcome. Only cohorts of individuals healthy at baseline were considered eligible. STUDY APPRAISAL AND SYNTHESIS METHODS: Extracted data included study population and location, sample size, population characteristics (age and sex), follow-up in years, walking or cycling exposure, mortality outcome, and adjustment for other co-variables. We used random-effects meta-analyses to investigate the beneficial effects of regular walking and cycling. RESULTS: Walking (18 results from 14 studies) and cycling (8 results from 7 studies) were shown to reduce the risk of all-cause mortality, adjusted for other PA. For a standardised dose of 11.25 MET.hours per week (or 675 MET.minutes per week), the reduction in risk for ACM was 11% (95% CI = 4 to 17%) for walking and 10% (95% CI = 6 to 13%) for cycling. The estimates for walking are based on 280,000 participants and 2.6 million person-years and for cycling they are based on 187,000 individuals and 2.1 million person-years. The shape of the dose-response relationship was modelled through meta-analysis of pooled relative risks within three exposure intervals. The dose-response analysis showed that walking or cycling had the greatest effect on risk for ACM in the first (lowest) exposure interval. CONCLUSIONS AND IMPLICATIONS: The analysis shows that walking and cycling have population-level health benefits even after adjustment for other PA. Public health approaches would have the biggest impact if they are able to increase walking and cycling levels in the groups that have the lowest levels of these activities. REVIEW REGISTRATION: The review protocol was registered with PROSPERO (International database of prospectively registered systematic reviews in health and social care) PROSPERO 2013: CRD42013004266

Dizajniranje i vrednovanje okularnih umetaka moksifloksacin hidroklorida

The objective of the present investigation was to prepare and evaluate ocular inserts of moxifloxacin. An ocular insert was made from an aqueous dispersion of moxifloxacin, sodium alginate, polyvinyl alcohol, and dibutyl phthalate by the film casting method. The ocular insert (5.5 mm diameter) was cross-linked by CaCl2 and was coated with Eudragit S-100, RL-100, RS-100, E-100 or Eudragit L-100. The in vitro drug drainage/permeation studies were carried out using an all-glass modified Franz diffusion cell. The drug concentration and mucoadhesion time of the ocular insert were found satisfactory. Cross-linking and coating with polymers extended the drainage from inserts. The cross-linked ocular insert coated with Eudragit RL-100 showed maximum drug permeation compared to other formulations.Cilj rada bio je priprava i evaluacija okularnih umetaka moksifloksacina. Okularni umetak izrađen je od vodene suspenzije moksifloksacina, natrijevog alginata, polivinilnog alkohola i dibutil-ftalata metodom odlijevanja filma. Okularni umetak (promjera 5,5 mm) umrežen je pomoću CaCl2 i obložen Eudragitom S-100, RL-100, RS-100, E-100 ili Eudragit L-100. In vitro drenaža/permeacija lijeka proučavana je koristeći staklenu modificiranu Franzovu difuzijsku ćeliju. Koncentracija lijeka i vrijeme mukoadhezije okularnih umetaka bili su zadovoljavajući. Umrežavanje i oblaganje polimerima produljilo je drenažu iz umetaka. Umreženi okularni umetci obloženi s Eudragit RL-100 pokazali su veću permeaciju lijeka u odnosu na ostale pripravke

Pointfree factorization of operation refinement

The standard operation refinement ordering is a kind of “meet of op- posites”: non-determinism reduction suggests “smaller” behaviour while increase of definition suggests “larger” behaviour. Groves’ factorization of this ordering into two simpler relations, one per refinement concern, makes it more mathe- matically tractable but is far from fully exploited in the literature. We present a pointfree theory for this factorization which is more agile and calculational than the standard set-theoretic approach. In particular, we show that factorization leads to a simple proof of structural refinement for arbitrary parametric types and ex- ploit factor instantiation across different subclasses of (relational) operation. The prospect of generalizing the factorization to coalgebraic refinement is discussedFundação para a Ciência e a Tecnologia (FCT) - PURE Project (Program Understanding and Re-engineering: Calculi and Applications), contract POSI/ICHS/44304/2002

Relationship between Structure, Entropy and Diffusivity in Water and Water-like Liquids

Anomalous behaviour of the excess entropy ($S_e$) and the associated scaling relationship with diffusivity are compared in liquids with very different underlying interactions but similar water-like anomalies: water (SPC/E and TIP3P models), tetrahedral ionic melts (SiO$_2$ and BeF$_2$) and a fluid with core-softened, two-scale ramp (2SRP) interactions. We demonstrate the presence of an excess entropy anomaly in the two water models. Using length and energy scales appropriate for onset of anomalous behaviour, the density range of the excess entropy anomaly is shown to be much narrower in water than in ionic melts or the 2SRP fluid. While the reduced diffusivities ($D^*$) conform to the excess entropy scaling relation, $D^* =A\exp (\alpha S_e)$ for all the systems (Y. Rosenfeld, Phys. Rev. A {\bf 1977}, {\it 15}, 2545), the exponential scaling parameter, $\alpha$, shows a small isochore-dependence in the case of water. Replacing $S_e$ by pair correlation-based approximants accentuates the isochore-dependence of the diffusivity scaling. Isochores with similar diffusivity scaling parameters are shown to have the temperature dependence of the corresponding entropic contribution. The relationship between diffusivity, excess entropy and pair correlation approximants to the excess entropy are very similar in all the tetrahedral liquids.Comment: 24 pages, 4 figures, to be published in Journal of Physical Chemistry

Formalising the Continuous/Discrete Modeling Step

Formally capturing the transition from a continuous model to a discrete model is investigated using model based refinement techniques. A very simple model for stopping (eg. of a train) is developed in both the continuous and discrete domains. The difference between the two is quantified using generic results from ODE theory, and these estimates can be compared with the exact solutions. Such results do not fit well into a conventional model based refinement framework; however they can be accommodated into a model based retrenchment. The retrenchment is described, and the way it can interface to refinement development on both the continuous and discrete sides is outlined. The approach is compared to what can be achieved using hybrid systems techniques.Comment: In Proceedings Refine 2011, arXiv:1106.348

Electronic Entropy Change in Ni-doped FeRh

The net entropy change corresponding to the free charge carriers in a Ni-doped FeRh bulk polycrystal was experimentally evaluated in a single sample using low-temperature heat capacity experiments with applied magnetic field and using Seebeck effect and Hall coefficient measurements at high temperatures across the first-order phase transition. From the heat capacity data, a value for the electronic entropy change ΔSel≈8.9 J kg−1K−1 was extracted. The analysis of the Seebeck coefficient allows tracing the change of the electronic entropy jump with applied magnetic field directly across the transition. The difference in electronic entropy contribution obtained is as high as 10% from 0.1 to 6 T. © 2019 Elsevier Ltd.The authors thank Dr. Sebastian Fahler for insightful discussions. TU Darmstadt acknowledges funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant no. 743116 project Cool Innov)