ESH-ESC guidelines for the management of hypertension.

The following is a brief statement of the 2003 European Society of Hypertension (ESH)-European Society of Cardiology (ESC) guidelines for the management of arterial hypertension.The continuous relationship between the level of blood pressure and cardiovascular risk makes the definition of hypertension arbitrary. Since risk factors cluster in hypertensive individuals, risk stratification should be made and decision about the management should not be based on blood pressure alone, but also according to the presence or absence of other risk factors, target organ damage, diabetes, and cardiovascular or renal damage, as well as on other aspects of the patient's personal, medical and social situation. Blood pressure values measured in the doctor's office or the clinic should commonly be used as reference. Ambulatory blood pressure monitoring may have clinical value, when considerable variability of office blood pressure is found over the same or different visits, high office blood pressure is measured in subjects otherwise at low global cardiovascular risk, there is marked discrepancy between blood pressure values measured in the office and at home, resistance to drug treatment is suspected, or research is involved. Secondary hypertension should always be investigated.The primary goal of treatment of patient with high blood pressure is to achieve the maximum reduction in long-term total risk of cardiovascular morbidity and mortality. This requires treatment of all the reversible factors identified, including smoking, dislipidemia, or diabetes, and the appropriate management of associated clinical conditions, as well as treatment of the raised blood pressure per se. On the basis of current evidence from trials, it can be recommended that blood pressure, both systolic and diastolic, be intensively lowered at least below 140/90 mmHg and to definitely lower values, if tolerated, in all hypertensive patients, and below 130/80 mmHg in diabetics.Lifestyle measures should be instituted whenever appropriate in all patients, including subjects with high normal blood pressure and patients who require drug treatment. The purpose is to lower blood pressure and to control other risk factors and clinical conditions present.In most, if not all, hypertensive patients, therapy should be started gradually, and target blood pressure achieved progressively through several weeks. To reach target blood pressure, it is likely that a large proportion of patients will require combination therapy with more than one agent. The main benefits of antihypertensive therapy are due to lowering of blood pressure per se. There is also evidence that specific drug classes may differ in some effect or in special groups of patients. The choice of drugs will be influenced by many factors, including previous experience of the patient with antihypertensive agents, cost of drugs, risk profile, presence or absence of target organ damage, clinical cardiovascular or renal disease or diabetes, patient's preference.

Optimization strategies for fast detection of positive selection on phylogenetic trees.

MOTIVATION: The detection of positive selection is widely used to study gene and genome evolution, but its application remains limited by the high computational cost of existing implementations. We present a series of computational optimizations for more efficient estimation of the likelihood function on large-scale phylogenetic problems. We illustrate our approach using the branch-site model of codon evolution. RESULTS: We introduce novel optimization techniques that substantially outperform both CodeML from the PAML package and our previously optimized sequential version SlimCodeML. These techniques can also be applied to other likelihood-based phylogeny software. Our implementation scales well for large numbers of codons and/or species. It can therefore analyse substantially larger datasets than CodeML. We evaluated FastCodeML on different platforms and measured average sequential speedups of FastCodeML (single-threaded) versus CodeML of up to 5.8, average speedups of FastCodeML (multi-threaded) versus CodeML on a single node (shared memory) of up to 36.9 for 12 CPU cores, and average speedups of the distributed FastCodeML versus CodeML of up to 170.9 on eight nodes (96 CPU cores in total).Availability and implementation: ftp://ftp.vital-it.ch/tools/FastCodeML/. CONTACT: selectome@unil.ch or nicolas.salamin@unil.ch.

Integrating life cycle costs and environmental impacts of composite rail car-bodies for a Korean train

Background, aim, and scope A coupled Life Cycle Costing and life cycle assessment has been performed for car-bodies of the Korean Tilting Train eXpress (TTX) project using European and Korean databases, with the objective of assessing environmental and cost performance to aid materials and process selection. More specifically, the potential of polymer composite car-body structures for the Korean Tilting Train eXpress (TTX) has been investigated. Materials and methods This assessment includes the cost of both carriage manufacturing and use phases, coupled with the life cycle environmental impacts of all stages from raw material production, through carriage manufacture and use, to end-of-life scenarios. Metallic carriages were compared with two composite options: hybrid steel-composite and full-composite carriages. The total planned production for this regional Korean train was 440 cars, with an annual production volume of 80 cars. Results and discussion The coupled analyses were used to generate plots of cost versus energy consumption and environmental impacts. The results show that the raw material and manufacturing phase costs are approximately half of the total life cycle costs, whilst their environmental impact is relatively insignificant (3-8%). The use phase of the car-body has the largest environmental impact for all scenarios, with near negligible contributions from the other phases. Since steel rail carriages weigh more (27-51%), the use phase cost is correspondingly higher, resulting in both the greatest environmental impact and the highest life cycle cost. Compared to the steel scenario, the hybrid composite variant has a lower life cycle cost (16%) and a lower environmental impact (26%). Though the full composite rail carriage may have the highest manufacturing cost, it results in the lowest total life cycle costs and lowest environmental impacts. Conclusions and recommendations This coupled cost and life cycle assessment showed that the full composite variant was the optimum solution. This case study showed that coupling of technical cost models with life cycle assessment offers an efficient route to accurately evaluate economic and environmental performance in a consistent way.

The establishment of communication systems depends on the scale of competition

How communication systems emerge and remain stable is an important question in both cognitive science and evolutionary biology. For communication to arise, not only must individuals cooperate by signaling reliable information, but they must also coordinate and perpetuate signals. Most studies on the emergence of communication in humans typically consider scenarios where individuals implicitly share the same interests. Likewise, most studies on human cooperation consider scenarios where shared conventions of signals and meanings cannot be developed de novo. Here, we combined both approaches with an economic experiment where participants could develop a common language, but under different conditions fostering or hindering cooperation. Participants endeavored to acquire a resource through a learning task in a computer-based environment. After this task, participants had the option to transmit a signal (a color) to a fellow group member, who would subsequently play the same learning task. We varied the way participants competed with each other (either global scale or local scale) and the cost of transmitting a signal (either costly or noncostly) and tracked the way in which signals were used as communication among players. Under global competition, players signaled more often and more consistently, scored higher individual payoffs, and established shared associations of signals and meanings. In addition, costly signals were also more likely to be used under global competition; whereas under local competition, fewer signals were sent and no effective communication system was developed. Our results demonstrate that communication involves both a coordination and a cooperative dilemma and show the importance of studying language evolution under different conditions influencing human cooperation.

Medical and pharmacological direct costs of a 9-week smoking cessation programme.

Background: Medical and pharmacological direct costs of cigarette smoking cessation programmes are not covered by health insurance in several countries despite documented cost-effectiveness. Design: prospective cost identification study of a 9-week programme in Switzerland. Methods: A total of 481 smokers were followed-up for 9 weeks. Socio-demographic characteristics, number of outpatient visits, dosage and frequency of use of nicotine replacement therapy (NRT) as well as date of relapse were prospectively collected. Individual cost of care until relapse or programme end as well as cost per week of follow-up were computed. Comparisons were carried out between the groups with or without relapse at the end of the programme. Results: Of the 209 men and 272 women included, 347 patients (72%) finished the programme. Among them, 240 patients (70%) succeeded in quitting and 107 patients (30%) relapsed. As compared with the group relapsing by the end of the programme, the group succeeding in quitting was more often living in a couple (68% vs. 55%, p = 0.029). Their mean weekly costs of visits were higher (CHF 81.2 ± 6.1 vs. 78.4 ± 7.6, p = 0.001), while their mean weekly costs for NRT were similar (CHF 24.2 ± 12.6 vs. 25.4 ± 15.9, p = 0.711). Mean total costs per week were similar (CHF 105.4 ± 15.4 vs. 103.8 ± 19.4, p = 0.252). More intensive NRT at week 4 increased the probability not to relapse at the end of the programme. Conclusions: Over 9 weeks, medical and pharmacological costs of stopping smoking are low. Good medical and social support as well as adequate NRT seem to play a role in successful quitting.

Costs of female reproduction in a conifer tree: a whole-tree level assessment

1. Costs of reproduction lie at the core of basic ecological and evolutionary theories, and their existence is commonly invoked to explain adaptive processes. Despite their sheer importance, empirical evidence for the existence and quantification of costs of reproduction in tree species comes mostly from correlational studies, while more comprehensive approaches remain missing. Manipulative experiments are a preferred approach to study cost of reproduction, as they allow controlling for otherwise inherent confounding factors like size or genetic background. 2. Here, we conducted a manipulative experiment in a Pinus halepensis common garden, removing developing cones from a group of trees and comparing growth and reproduction after treatment with a control group. We also estimated phenotypic and genetic correlations between reproductive and vegetative traits. 3. Manipulated trees grew slightly more than control trees just after treatment, with just a transient, marginally non-significant difference. By contrast, larger differences were observed for the number of female cones initiated 1 year after treatment, with an increase of 70% more cones in the manipulated group. Phenotypic and genetic correlations showed that smaller trees invested a higher proportion of their resources in reproduction, compared with larger trees, which could be interpreted as an indirect evidence for costs of reproduction. 4. Synthesis. This research showed a high impact of current reproduction on reproductive potential, even when not significant on vegetative growth. This has strong implications for how we understand adaptive strategies in forest trees and should encourage further interest on their still poorly known reproductive life-history traits.

Inter-limb coordination and energy cost in swimming.

OBJECTIVES: This study investigated the relationship between inter-arm coordination and the energy cost of locomotion in front crawl and breaststroke and explored swimmers' flexibility in adapting their motor organization away from their preferred movement pattern. DESIGN: Nine front-crawlers performed three 300-m in front crawl and 8 breaststrokers performed three 200-m in breaststroke at constant submaximal intensity and with 5-min rests. Each trial was performed randomly in a different coordination pattern: freely chosen, 'maximal glide' and 'minimal glide'. Two underwater cameras videotaped frontal and side views to analyze speed, stroke rate, stroke length and inter-limb coordination. METHODS: In front crawl, inter-arm coordination was quantified by the index of coordination (IdC) and the leg beat kicks were counted. In breaststroke, four time gaps quantified the arm to leg coordination (i.e., time between leg and arm propulsions; time between beginning, 90° flexion and end of arm and leg recoveries). The energy cost of locomotion was calculated from gas exchanges and blood lactate concentration. RESULTS: In both front crawl and breaststroke, the freely chosen coordination corresponded to glide pattern and showed the lowest energy cost (12.8 and 17.1Jkg(-1)m(-1), respectively). Both front-crawlers and breaststrokers were able to reach 'maximal glide' condition (respectively, +35% and +28%) but not 'minimal glide' condition for front crawl. CONCLUSIONS: The freely chosen pattern appeared more economic because more trained. When coordination was constrained, the swimmers had higher coordination flexibility in breaststroke than in front crawl, suggesting that breaststroke coordination was easier to regulate by changing glide time.

Persistence of Transmitted HIV-1 Drug Resistance Mutations Associated with Fitness Costs and Viral Genetic Backgrounds.

Transmission of drug-resistant pathogens presents an almost-universal challenge for fighting infectious diseases. Transmitted drug resistance mutations (TDRM) can persist in the absence of drugs for considerable time. It is generally believed that differential TDRM-persistence is caused, at least partially, by variations in TDRM-fitness-costs. However, in vivo epidemiological evidence for the impact of fitness costs on TDRM-persistence is rare. Here, we studied the persistence of TDRM in HIV-1 using longitudinally-sampled nucleotide sequences from the Swiss-HIV-Cohort-Study (SHCS). All treatment-naïve individuals with TDRM at baseline were included. Persistence of TDRM was quantified via reversion rates (RR) determined with interval-censored survival models. Fitness costs of TDRM were estimated in the genetic background in which they occurred using a previously published and validated machine-learning algorithm (based on in vitro replicative capacities) and were included in the survival models as explanatory variables. In 857 sequential samples from 168 treatment-naïve patients, 17 TDRM were analyzed. RR varied substantially and ranged from 174.0/100-person-years;CI=[51.4, 588.8] (for 184V) to 2.7/100-person-years;[0.7, 10.9] (for 215D). RR increased significantly with fitness cost (increase by 1.6[1.3,2.0] per standard deviation of fitness costs). When subdividing fitness costs into the average fitness cost of a given mutation and the deviation from the average fitness cost of a mutation in a given genetic background, we found that both components were significantly associated with reversion-rates. Our results show that the substantial variations of TDRM persistence in the absence of drugs are associated with fitness-cost differences both among mutations and among different genetic backgrounds for the same mutation.

Energetics and mechanics of walking in patients with chronic low back pain and healthy matched controls.

PURPOSE: Walking in patients with chronic low back pain (cLBP) is characterized by motor control adaptations as a protective strategy against further injury or pain. The purpose of this study was to compare the preferred walking speed, the biomechanical and the energetic parameters of walking at different speeds between patients with cLBP and healthy men individually matched for age, body mass and height. METHODS: Energy cost of walking was assessed with a breath-by-breath gas analyser; mechanical and spatiotemporal parameters of walking were computed using two inertial sensors equipped with a triaxial accelerometer and gyroscope and compared in 13 men with cLBP and 13 control men (CTR) during treadmill walking at standard (0.83, 1.11, 1.38, 1.67 m s(-1)) and preferred (PWS) speeds. Low back pain intensity (visual analogue scale, cLBP only) and perceived exertion (Borg scale) were assessed at each walking speed. RESULTS: PWS was slower in cLBP [1.17 (SD = 0.13) m s(-1)] than in CTR group [1.33 (SD = 0.11) m s(-1); P = 0.002]. No significant difference was observed between groups in mechanical work (P ≥ 0.44), spatiotemporal parameters (P ≥ 0.16) and energy cost of walking (P ≥ 0.36). At the end of the treadmill protocol, perceived exertion was significantly higher in cLBP [11.7 (SD = 2.4)] than in CTR group [9.9 (SD = 1.1); P = 0.01]. Pain intensity did not significantly increase over time (P = 0.21). CONCLUSIONS: These results do not support the hypothesis of a less efficient walking pattern in patients with cLBP and imply that high walking speeds are well tolerated by patients with moderately disabling cLBP.

Ability of physicians to diagnose influenza and usefulness of a rapid influenza antigen test in febrile returning travelers: A randomized controlled trial.

BACKGROUND: Fever is a frequent cause of medical consultation among returning travelers. The objectives of this study were to assess whether physicians were able to identify patients with influenza and whether the use of an influenza rapid diagnostic test (iRDT) modified the clinical management of such patients. METHODS: Randomized controlled trial conducted at 2 different Swiss hospitals between December 2008 and November 2012. Inclusion criteria were 1) age ≥18 years, 2) documented fever of ≥38 °C or anamnestic fever + cough or sore throat within the last 4 days, 3) illness occurring within 14 days after returning from a trip abroad, 4) no definitive alternative diagnosis. Physicians were asked to estimate the likelihood of influenza on clinical grounds, and a single nasopharyngeal swab was taken. Thereafter patients were randomized into 2 groups: i) patients with iRDT (BD Directigen A + B) performed on the nasopharyngeal swab, ii) patients receiving usual care. A quantitative PCR to detect influenza was done on all nasopharyngeal swabs after the recruitment period. Clinical management was evaluated on the basis of cost of medical care, number of X-rays requested and prescription of anti-infective drugs. RESULTS: 100 eligible patients were referred to the investigators. 93 patients had a naso-pharyngeal swab for a PCR and 28 (30%) swabs were positive for influenza. The median probability of influenza estimated by the physician was 70% for the PCR positive cases and 30% for the PCR negative cases (p < 0.001). The sensitivity of the iRDT was only 20%, and specificity 100%. Mean medical cost for the patients managed with iRDT and without iRDT were USD 581 (95%CI 454-707) and USD 661 (95%CI 522-800) respectively. 14/60 (23%) of the patients managed with iRDT were prescribed antibiotics versus 13/33 (39%) in the control group (p = 0.15). No patient received antiviral treatment. CONCLUSION: Influenza was a frequent cause of fever among these febrile returning travelers. Based on their clinical assessment, physicians had a higher level of suspicion for influenza in PCR positive cases. The iRDT used in this study showed a disappointingly low sensitivity and can therefore not be recommended for the management of these patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT00821626.

Sex- and melanism-specific variations in the oxidative status of adult tawny owls in response to manipulated reproductive effort.

Oxidative stress, determined by the balance between the production of damaging reactive oxygen species (ROS) and antioxidant defences, is hypothesized to play an important role in shaping the cost of reproduction and life history trade-offs. To test this hypothesis, we manipulated reproductive effort in 94 breeding pairs of tawny owls (Strix aluco) to investigate the sex- and melanism-specific effects on markers of oxidative stress in red blood cells (RBCs). This colour polymorphic bird species shows sex-specific division of labour and melanism-specific history strategies. Brood sizes at hatching were experimentally enlarged or reduced to increase or decrease reproductive effort, respectively. We obtained an integrative measure of the oxidative balance by measuring ROS production by RBCs, intracellular antioxidant glutathione levels and membrane resistance to ROS. We found that light melanic males (the sex undertaking offspring food provisioning) produced more ROS than darker conspecifics, but only when rearing an enlarged brood. In both sexes, light melanic individuals had also a larger pool of intracellular antioxidant glutathione than darker owls under relaxed reproductive conditions (i.e. reduced brood), but not when investing substantial effort in current reproduction (enlarged brood). Finally, resistance to oxidative stress was differently affected by the brood size manipulation experiment in males and females independently of their plumage coloration. Altogether, our results support the hypothesis that reproductive effort can alter the oxidative balance in a sex- and colour-specific way. This further emphasizes the close link between melanin-based coloration and life history strategies.

Experimental enhancement of corticosterone levels positively affects subsequent male survival.

Corticosterone is an important hormone of the stress response that regulates physiological processes and modifies animal behavior. While it positively acts on locomotor activity, it may negatively affect reproduction and social activity. This suggests that corticosterone may promote behaviors that increase survival at the cost of reproduction. In this study, we experimentally investigate the link between corticosterone levels and survival in adult common lizards (Lacerta vivipara) by comparing corticosterone-treated with placebo-treated lizards. We experimentally show that corticosterone enhances energy expenditure, daily activity, food intake, and it modifies the behavioral time budget. Enhanced appetite of corticosterone-treated individuals compensated for increased energy expenditure and corticosterone-treated males showed increased survival. This suggests that corticosterone may promote behaviors that reduce stress and it shows that corticosterone per se does not reduce but directly or indirectly increases longer-term survival. This suggests that the production of corticosterone as a response to a stressor may be an adaptive mechanism that even controls survival.

Future development of gastrointestinal cancer incidence and mortality rates in Switzerland: a tumour registry- and population-based projection up to 2030.

QUESTIONS UNDER STUDY: Since tumour burden consumes substantial healthcare resources, precise cancer incidence estimations are pivotal to define future needs of national healthcare. This study aimed to estimate incidence and mortality rates of oesophageal, gastric, pancreatic, hepatic and colorectal cancers up to 2030 in Switzerland. METHODS: Swiss Statistics provides national incidences and mortality rates of various cancers, and models of future developments of the Swiss population. Cancer incidences and mortality rates from 1985 to 2009 were analysed to estimate trends and to predict incidence and mortality rates up to 2029. Linear regressions and Joinpoint analyses were performed to estimate the future trends of incidences and mortality rates. RESULTS: Crude incidences of oesophageal, pancreas, liver and colorectal cancers have steadily increased since 1985, and will continue to increase. Gastric cancer incidence and mortality rates reveal an ongoing decrease. Pancreatic and liver cancer crude mortality rates will keep increasing, whereas colorectal cancer mortality on the contrary will fall. Mortality from oesophageal cancer will plateau or minimally increase. If we consider European population-standardised incidence rates, oesophageal, pancreatic and colorectal cancer incidences are steady. Gastric cancers are diminishing and liver cancers will follow an increasing trend. Standardised mortality rates show a diminution for all but liver cancer. CONCLUSIONS: The oncological burden of gastrointestinal cancer will significantly increase in Switzerland during the next two decades. The crude mortality rates globally show an ongoing increase except for gastric and colorectal cancers. Enlarged healthcare resources to take care of these complex patient groups properly will be needed.

The forced adoption of a fast-track appraisal process for a breast cancer treatment in UK

Trastuzumab (Herceptin ®, Roche) is approved in UK for the treatment of the metastatic breast cancer since 2001. As of 2005, concomitantly with the publication of 3 studies that showed it produces a 50% reduction of the recurrence rates of breast cancer, trastuzumab started to be prescribed in the earlt adjuvant treatrnent of this disease. Und June 2006, trastuzumab did not have both: 1) regulatory approval and 2) NICE [National Institute for Health and Clinical Excellence] recommendation for the use in early stages of breast cancer. During the period until June 2006, the trastuzumab use in those patients was not reimbursed and because the cost of trastuzumab is equal with the yearly UK average income, most of patients could not self fund their treatrnent. Before the publication of the final NICE guidance, the new data of trastuzumab in early breast cancer raised enormous patient and professional interest and expectations. A great volume of public and professional pressure was generated to transcend a system by which Primary Care Trusts can reimburse a treatment only after a formal guidance was issued. This paper draw on a case study depicting and analyzing the process by which regulatory approval and NICE recommendations were achieved in a record time and how trastuzumab became a standard treatment on early adjuvant breast cancer. According to the data we gathered in this work we were witnessing one of the fastest processes of adoption of a health care technology since the creation of NICE, in 1999. This study addresses the following research question: How and why does the adoption pattern of trastuzumab differ from the rational decision-making model of the reimbursement process in UK? [Author, p. 4]

Worldwide trends in diabetes since 1980: a pooled analysis of 751 population-based studies with 4.4 million participants.

One of the global targets for non-communicable diseases is to halt, by 2025, the rise in the age-standardised adult prevalence of diabetes at its 2010 levels. We aimed to estimate worldwide trends in diabetes, how likely it is for countries to achieve the global target, and how changes in prevalence, together with population growth and ageing, are affecting the number of adults with diabetes. We pooled data from population-based studies that had collected data on diabetes through measurement of its biomarkers. We used a Bayesian hierarchical model to estimate trends in diabetes prevalence-defined as fasting plasma glucose of 7.0 mmol/L or higher, or history of diagnosis with diabetes, or use of insulin or oral hypoglycaemic drugs-in 200 countries and territories in 21 regions, by sex and from 1980 to 2014. We also calculated the posterior probability of meeting the global diabetes target if post-2000 trends continue. We used data from 751 studies including 4,372,000 adults from 146 of the 200 countries we make estimates for. Global age-standardised diabetes prevalence increased from 4.3% (95% credible interval 2.4-7.0) in 1980 to 9.0% (7.2-11.1) in 2014 in men, and from 5.0% (2.9-7.9) to 7.9% (6.4-9.7) in women. The number of adults with diabetes in the world increased from 108 million in 1980 to 422 million in 2014 (28.5% due to the rise in prevalence, 39.7% due to population growth and ageing, and 31.8% due to interaction of these two factors). Age-standardised adult diabetes prevalence in 2014 was lowest in northwestern Europe, and highest in Polynesia and Micronesia, at nearly 25%, followed by Melanesia and the Middle East and north Africa. Between 1980 and 2014 there was little change in age-standardised diabetes prevalence in adult women in continental western Europe, although crude prevalence rose because of ageing of the population. By contrast, age-standardised adult prevalence rose by 15 percentage points in men and women in Polynesia and Micronesia. In 2014, American Samoa had the highest national prevalence of diabetes (>30% in both sexes), with age-standardised adult prevalence also higher than 25% in some other islands in Polynesia and Micronesia. If post-2000 trends continue, the probability of meeting the global target of halting the rise in the prevalence of diabetes by 2025 at the 2010 level worldwide is lower than 1% for men and is 1% for women. Only nine countries for men and 29 countries for women, mostly in western Europe, have a 50% or higher probability of meeting the global target. Since 1980, age-standardised diabetes prevalence in adults has increased, or at best remained unchanged, in every country. Together with population growth and ageing, this rise has led to a near quadrupling of the number of adults with diabetes worldwide. The burden of diabetes, both in terms of prevalence and number of adults affected, has increased faster in low-income and middle-income countries than in high-income countries. Wellcome Trust.