Direct Contraction Research Articles

Hyperbolic spaces and directional contractions

The axiomatic approach to metric convexity goes back to the pioneering work of Karl Menger in 1928. This is an overview of this concept and the role it plays in metric fixed point theory especially in conjunction with spaces possessing a “hyperbolic” type structures. These include the CAT(0) spaces, hyperconvex metric spaces, and [Formula: see text]-trees. Much of the discussion involves the existence of “approximate” fixed point sequences for mappings satisfying weak contractive conditions. Applications of a well-known fixed point theorem due to Caristi are also included. These involve fixed and approximate fixed points for mappings satisfying local “directional” contractive and non-expansive conditions. Convexity plays a role in this part of the discussion as well. While the paper is semi-expository in nature, some detailed proofs appear here for the first time. Also the concept of a weak [Formula: see text]-directional contraction introduced in Sec. 8 appears to be new. Several suggestions for further research are also discussed.

A Hollow Polyethylene Fiber-Based Artificial Muscle

Recently, researches on artificial muscles for imitating the functions of the natural muscles has attracted wide attention. The fiber-shape actuators, shape-memory materials or deforming devices, which are similar to human muscle fiber bundles, have extensively studied and provided more possibilities for artificial muscles. Herein, we develop a thermal responsible fiber-shaped actuator based on the low-cost hollow polyethylene fiber. The sheath-core structured fibrous actuators and the stainless-steel conductive yarn winded pre-stretched polyethylene actuators are fabricated with the heating assisted pre-stretching procedure. The actuation mechanism of the thermal-responsive orientation change of molecular chains driving the actuation is discussed and demonstrated by 2D XRD patterns. These polyethylene-based fibrous actuators displayed three significant advantages including (i) color-turning and shape-changing bifunctional response, (ii) direct joule heating actuation and (iii) effective contraction (18% shrinkage of the pristine length) and lifting ability (the ratio of lifting weight to self-weight is up to 50).

Incentive Contracts for Capacity Restoration Under Risk of Supply Disruption

We consider a supply chain consisting of a supplier and a buyer. The buyer faces demand as a function of the selling price. There is risk of supply disruption, but the supplier can rebuild his capacity if he has invested for the capacity restoration before a disruption. To motivate the supplier to invest, the buyer can use one of two incentive contracts, namely direct and indirect . With a direct contract, the buyer provides a financial subsidy to share the supplier's capacity restoration cost when disruption occurs. With an indirect contract, the buyer adjusts the wholesale price in the case of disruption to stimulate the capacity restoration. Both contracts allow the buyer to adjust the order quantity in the case of disruption. We analyze decisions of each supply chain member under the two contracts with different commitment strategies (the ex ante commitment (EA) strategy under which the contract is signed before disruption and the ex post commitment (EP) strategy under which the contract is signed after disruption), and study how the supply disruption affects the buyer's selling price to end customers. We show that, from the perspective of either the supplier or the buyer, the incentive contract under the EA strategy is preferred by leading to a greater profit. Further, through numerical experiments, we recognize conditions for the fixed investment cost, probability of disruption, and regular wholesale price, under which each incentive contract encourages the supplier to invest for the capacity restoration, and brings greater profit to each supply chain member.

Bi-Material Negative Thermal Expansion Inverted Trapezoid Lattice based on A Composite Rod.

Negative thermal expansion (NTE) lattices are widely used in aerospace engineering where the structures experience large temperature variation. However, the available range of NTE of the current lattices is quite narrow, which severely limits their engineering application. In this paper, we report an inverted trapezoid lattice (ITL) with large NTE. The NTE of the ITL is 2.6 times that of a typical triangular lattice with the same height and hypotenuse angle. Theoretically, with a pin-jointed assumption, the ITL can improve the NTE by order of magnitude if the length ratio of the composite rod is changed. In the presented ITL, a composite rod is utilized as the base of the ITL. The composite rod has large inner NTE. The inverted trapezoid structure converts the inner NTE to the vertical direction contraction and obtains an extra NTE. Finite element simulations and experimental verification by interferometric measurement were conducted to verify the large thermal expansion of the ITL.

1691 Value Based Healthcare in MIGS; Bundles and Beyond

Study Objective Providing High Quality Outcomes in Minimally Invasive Gynecology Surgery to Satisfy the Triple Aim of CMS; Quality, Cost, and Patient Experience Design Retrospective Cohort at multiple institutions, Savings and Outcome Data (complications, readmissions, infection rate), Proof of Concept and Feasibility of Creating National Network with Alternative Payment Model (APM) Setting Ambulatory Surgery Centers in multiple cities Patients or Participants Non-Randomized retrospective review of program growth Interventions Laparoscopic Hysterectomy performed with Same Day Discharge home in ASC setting, each location with one primary surgeon in charge of quality for site. Aggregation of outcome data, cost, charges, and savings achieved with review of CMS reference based priced. Measurements and Main Results LH (Laparoscopic Hysterectomy) was performed in an ambulatory surgery center setting by several physicians at respective institutions in Portland OR, Atlanta GA, Minneapolis MN, Phoenix AZ, Houston TX, Dallas TX, Chicago IL, and New York City NY. Cases were referred to a High Performance Network of surgeons from self-insured companies interested in direct contracts outside of traditional commercial contracts. 200 Patients were referred to the provider network and underwent LH at one of several locations. Bundled pricing was provided with indemnification against complications. All surgeons performed LH with same day discharge. Patient demographics, including age/BMI/procedure, will be provided at time of presentation. Outcomes and cost were compared to national standards for Gynecology Surgery. Conclusion Bundled Gynecologic Procedures provide a Cost Effective Value Based Solution in the US Healthcare System. Publication of such success is imperative in order to expand the opportunity for deployment of Advanced Alternative Payment Methodology as set forth by CMS in the Affordable Care Act. This retrospective multi-center cohort validates a hypothesis that an outpatient program of surgical bundles can be scaled and deployed nationally to provide higher quality outcomes, lower cost, and a better patient experience, the triple aim of Value Based Care.

Comparative Analysis of Direct Labour and Contracting System of Project Procurement

This study examines the performance of two project procurement methods commonly used in project construction, the direct labour and contracting system. Using cost, time and quality as assessment criteria, the work seek to determine possible advantage of one method over the other. Quasi-experimental design and questionnaire were combined to carry this study. Respondents was mainly officers and building contractors, key players in project procurement. Results obtained in this work showed that there was no significant difference between the two methods in terms of cost overrun, though overall cost was higher for the direct labour method. It also revealed a significant difference between time overrun for the two methods as direct method took longer time. The study concluded by emphasising the need for training, openness and empowerment. It also recommended the need for all establishments to adopt participatory project management through direct labour. Key Words : Direct Labour, Contract, Procurement, Time, Cost, Cost overrun, Time overrun DOI : 10.7176/CER/11-8-07 Publication date :September 30 th 2019

Elucidation With the Protease α-Chymotrypsin of the Inhibitory Modulating Action of Endogenous Neuropeptide Y Over Sympathetic Neurotransmission in Rat Vas Deferens

The physiological role of endogenous neuropeptide Y (NPY) in sympathetic neurotransmission was examined in rat and guinea pig vas deferens (VD), using α-chymotrypsin (α-cT). NPY-like immunoreactivity was detected in the longitudinal muscle layer of VD densely in rats but sparsely in guinea pigs, and it disappeared following surgical denervation. Under blockade of the prejunctional α2-adrenergic autoinhibition, α-cT potentiated the phasic contraction in rat, but not guinea pig, VD induced by trains of transmural nerve stimulation (TNS) in a frequency-dependent manner, which was reproducible during repeated applications and not affected by pretreatment with capsaicin. In contrast, α-cT did not potentiate the twitch response or contractions induced respectively by a single pulse TNS or by direct electrical stimulation to the smooth muscle. Exogenously applied NPY suppressed the twitch response, which was cancelled by α-cT, and excitatory junction potentials, although it affected neither spontaneous junction potentials nor the direct electrical stimulation-induced contraction. These observations provided further evidence to support that NPY is released endogenously by TNS at high frequency, acting prejunctionally to suppress sympathetic neurotransmission. Thus, the protease α-cT proved itself to be a useful tool to reveal a functional role of endogenously released peptides.

Modulation of the optical properties of zigzag silicene nanoribbons by double carbon chains

Using first-principles calculations, we investigate the electronic and optical properties of zigzag silicene nanoribbons substituted with double carbon chains. The results show that the chains are pulled nearly straight and produce a rather obvious transverse contraction in the width direction of the ribbon. The double carbon chains introduce defect states that appear as two degenerate bands across the Fermi level. These nanoribbons are always metallic regardless of the position of the carbon chains or the ribbon width. Under the same bandwidth, the imaginary parts of the dielectric functions in the Ex and Ey directions reveal red- and blue-shifts, respectively, with increasing distance between the two C chains. The imaginary parts of the dielectric functions in the Ex and Ey directions reveal blue- and redshifts, respectively, with increasing ribbon width. Three major peaks in the imaginary part of the dielectric function correspond to the intrinsic plasma frequencies originating from electron transitions of silicon and carbon. Such excellent electronic and optical properties may lead to some important applications of the nanoribbons in short-wavelength optoelectronic devices.

Gradient optimization of fermionic projected entangled pair states on directed lattices

The recently developed stochastic gradient method combined with Monte Carlo sampling techniques [PRB {\bf 95}, 195154 (2017)] offers a low scaling and accurate method to optimize the projected entangled pair states (PEPS). We extended this method to the fermionic PEPS (fPEPS). To simplify the implementation, we introduce a fermi arrow notation to specify the order of the fermion operators in the virtual entangled EPR pairs. By defining some local operation rules associated with the fermi arrows, one can implement fPEPS algorithms very similar to that of standard PEPS. We benchmark the method for the interacting spinless fermion models, and the t-J models. The numerical calculations show that the gradient optimization greatly improves the results of simple update method. Furthermore, much larger virtual bond dimensions ($D$) and truncation dimensions ($D_c$) than those of boson and spin systems are necessary to converge the results. The method therefore offer a powerful tool to simulate fermion systems because it has much lower scaling than the direct contraction methods.

Angiotensin II Regulates Excitability and Contractile Functions of Myocardium and Smooth Muscles through Autonomic Nervous Transmission

Angiotensin II (Ang II) is an intrinsic peptide having strong vasopressor effects, and thus, it plays an important role in the physiological regulation of blood pressure. The vasopressor effects of Ang II include direct contraction of myocardium and vascular smooth muscles (SMs) along with aldosterone-mediated sodium retention. In addition, indirect vascular contractions induced by noradrenaline (NA), the release of which is mediated through Ang II receptor type 1 (AT1) existing at the sympathetic nerve terminals (SNTs), also contribute to the vasopressor effects of Ang II. Stimulation of NA release from SNTs by Ang II also occurs in the myocardium leading to an increase in heart rate and cardiac contraction. Furthermore, Ang II enhances the contractions of non-vascular SMs, such as vas deferens, through induction of NA release from the SNTs. We have found that Ang II attenuated vagus nerve stimulation-induced bradycardia in a losartan-sensitive manner. This suggests that Ang II attenuates vagus nerve stimulation-induced bradycardia by inhibiting acetylcholine (ACh) release from the parasympathetic nerve terminals (PNTs) through activation of the AT1 receptor. Ang II was also reported to attenuate the release of ACh from the PNTs in SMs, such as stomach and airway, thus suppressing their contractile functions. There are, however, conflicting reports of the effects of Ang II on parasympathetic nerve-mediated contractile regulation of SMs. In this review, we have highlighted the relevant research articles including our experimental reports on the regulation of sympathetic and parasympathetic nerve-mediated excitation and contraction by Ang II along with the future prospects.

Sildenafil corrects the increased contractility of rat detrusor muscle induced by alprostadil in vitro

Sildenafil (PDE5-inhibitor) and alprostadil (PGE1) are used in combination clinically for the management of some cases of erectile dysfunction. Despite the roles of prostaglandins (PG) and nitric oxide (NO) pathways in contractility of bladder smooth muscle are frequently studied, the effect of sildenafil/alprostadil combination and the crosstalk between NO/cGMP and PG pathways on bladder activity is not documented. Organ-bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS, 4Hz, 80V, 1ms), respectively. The contractile responses in absence and presence of the tested drugs at different concentrations were compared. Results are expressed as mean ± SEM (n = 5-7). Alprostadil (0.01-10 μM) concentration-dependently potentiated ACh (100μM)- and EFS (4 Hz)- induced contraction. Maximum potentiation of ACh-contraction in presence of alprostadil was 40 ± 5%. Sildenafil potentiated ACh-induced contraction at low concentrations (0.01-1 μM), but inhibited it at higher ones (10-100 μM). IBMX (non-selective PDE-inhibitor, 0.01-100μM) and SNP (NO-donor, 1nM-1 mM) produced the same biphasic pattern. The potentiatory phase of sildenafil was inhibited by atropine (0.1μM), L-NAME (non-selective NOS-inhibitor, 100μM), N-PLA (nNOS-inhibitor, 30μM) or MB (nonselective GC-inhibitor, 10μM). In presence of sildenafil (0.1μM), the concentration-response curve of alprostadil (0.01-10μM) on both ACh and EFS-induced contraction was clearly shifted downward. A crosstalk between PGE1 and NO/cGMP pathways may exist. At low concentrations only, the effect of sildenafil on bladder contractility is dependent on NO/cGMP. cGMP intracellularly-elevated by sildenafil, may inhibit the activity of PLC and hence the cascade of EP1-receptors, thus masking the hyperactivity of bladder caused by alprostadil, which adds to the advantages of this combination.

Characterization of the gastric motility response to human motilin and erythromycin in human motilin receptor-expressing transgenic mice.

Motilin is a gastrointestinal peptide hormone that stimulates gastrointestinal motility. Motilin is produced primarily in the duodenum and jejunum. Motilin receptors (MTLRs) are G protein-coupled receptors that may represent a clinically useful pharmacological target as they can be activated by erythromycin. The functions of motilin are highly species-dependent and remain poorly understood. As a functional motilin system is absent in rodents such as rats and mice, these species are not commonly used for basic studies. In this study, we examine the usefulness of human MTLR-overexpressing transgenic (hMTLR-Tg) mice by identifying the mechanisms of the gastric motor response to human motilin and erythromycin.The distribution of hMTLR was examined immunohistochemically in male wild-type (WT) and hMTLR-Tg mice. The contractile response of gastric strips was measured isometrically in an organ bath, while gastric emptying was determined using phenol red.hMTLR expression was abundant in the gastric smooth muscle layer. Interestingly, higher levels of hMTLR expression were observed in the myenteric plexus of hMTLR-Tg mice but not WT mice. hMTLR was not co-localized with vesicular acetylcholine transporter, a marker of cholinergic neurons in the myenteric plexus. Treatment with human motilin and erythromycin caused concentration-dependent contraction of gastric strips obtained from hMTLR-Tg mice but not from WT mice. The contractile response to human motilin and erythromycin in hMTLR-Tg mice was affected by neither atropine nor tetrodotoxin and was totally absent in Ca2+-free conditions. Furthermore, intraperitoneal injection of erythromycin significantly promoted gastric emptying in hMTLR-Tg mice but not in WT mice.Human motilin and erythromycin stimulate gastric smooth muscle contraction in hMTLR-Tg mice. This action is mediated by direct contraction of smooth muscle via the influx of extracellular Ca2+. Thus, hMTLR-Tg mice may be useful for the evaluation of MTLR agonists as gastric prokinetic agents.

Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

The gut-brain peptide neuromedin U (NMU) decreases food intake and body weight and improves glucose tolerance. Here, we characterized NMU as an enteropeptide and determined how it impacts glucose excursion. NMU was expressed predominantly in the proximal small intestine, and its secretion was triggered by ingestion of a mixed meal. Although a single peripheral injection of NMU in C57BL/6NRj mice prevented the rise of glycemia upon an oral but not an intraperitoneal load of glucose, it unexpectedly prevented insulin secretion, only slightly improved peripheral insulin sensitivity, and barely reduced intestinal glucose absorption. Interestingly, peripheral administration of NMU abrogated gastric emptying. NMU receptors 1 and 2 were detected in pyloric muscles and NMU was able to directly induce pyloric contraction in a dose-dependent manner ex vivo in isometric chambers. Using a modified glucose tolerance test, we demonstrate that improvement of oral glucose tolerance by NMU was essentially, if not exclusively, because of its impact on gastric emptying. Part of this effect was abolished in vagotomized (VagoX) mice, suggesting implication of the vagus tone. Accordingly, peripheral injection of NMU was associated with increased number of c-FOS-positive neurons in the nucleus of the solitary tract, which was partly prevented in VagoX mice. Finally, NMU kept its ability to improve oral glucose tolerance in obese and diabetic murine models. Together, these data demonstrate that NMU is an enteropeptide that prevents gastric emptying directly by triggering pylorus contraction and indirectly through vagal afferent neurons. This blockade consequently reduces intestinal nutrient absorption and thereby results in an apparent improved tolerance to oral glucose challenge.-Jarry, A.-C., Merah, N., Cisse, F., Cayetanot, F., Fiamma, M.-N., Willemetz, A., Gueddouri, D., Barka, B., Valet, P., Guilmeau, S., Bado, A., Le Beyec, J., Bodineau, L., Le Gall, M. Neuromedin U is a gut peptide that alters oral glucose tolerance by delaying gastric emptying via direct contraction of the pylorus and vagal-dependent mechanisms.

Time-Dependent Complete Active Space Embedded in a Polarizable Force Field.

Electron correlation and environmental effects play important roles in electron dynamics and spectroscopic observables of chemical systems in condensed phase. In this paper, we present a time-dependent complete active space configuration interaction (TD-CASCI) approach embedded in a polarizable force field, MMPol. The present implementation of TD-CASCI/MMPol utilizes a direct matrix-vector contraction, allowing studies of large systems. This scheme is used to study the solvatochromic shift of coumarin 153 in methanol. The TD-CASCI/MMPol approach captures the double excitation character in the excited state wave function and accurately predicts the solvatochromic red-shift of coumarin 153 dye within the experimental range, outperforming linear response time-dependent density functional theory. The effect of using different reference orbitals for the TD-CASCI/MMPol simulation is also investigated, highlighting the need for an unbiased treatment of all electronic states in the energy range of interest.

Jumping and take-off in a winged scorpion fly (Mecoptera, Panorpa communis).

High-speed videos were used to analyse whether and how adults of a winged species of scorpion fly (Mecoptera, Panorpa communis) jump and determine whether they use the same mechanism as that of the only other mecopteran known to jump, the wingless snow flea, Boreus hyemalis Adult females are longer and heavier than males and have longer legs, but of the same relative proportions. The middle legs are 20% longer and the hind legs 60% longer than the front legs. A jump starts with the middle and hind legs in variable positions, but together, by depressing their coxo-trochanteral and extending their femoro-tibial joints, they accelerate the body in 16-19 ms to mean take-off velocities of 0.7-0.8 m s-1; performances in males and females were not significantly different. Depression of the wings accompanies these leg movements, but clipping them does not affect jump performance. Smooth transition to flapping flight occurs once airborne with little loss of energy to body rotation. Ninety percent of the jumps analysed occurred without an observable stimulus; the remaining 10% were in response to a mechanical touch. The performance of these jumps was not significantly different. In its fastest jumps, a scorpion fly experiences an acceleration of 10g , expends 23 µJ of energy and requires a power output less than 250 W kg-1 of muscle that can be met by direct muscle contractions without invoking an indirect power amplification mechanism. The jumping mechanism is like that of snow fleas.

Preliminary study of bamboo-like tree structure based on granular particle-spring model: Relaxation and tortuosity

Bamboo-like tree structure is modelled using granular particles connected with linear and bending springs. The first type of spring is responsible for contraction and relaxation in axial direction, while the second one is in angular direction. For simplicity the system is first considered only two-dimension in this work. Previous work showed that for two branches tree, wind influenced only one branch which has resonance with the wind velocity. Only relaxation stage is reported in this work, that can not yet achieved stable state.

Conclusion of direct contracts with utilities providers

The subject of the paper is conclusion and execution of direct contracts between consumers and utilities providers.The main aim of the paper is to confirm or disprove the hypothesis that direct contracts between consumers and utilities providers are more convenient for utilities providers than for consumers.The methodology of the study includes general scientific methods (analysis, synthesis, comparison, generalization, description) as well as particular academic legal methods (formal-legal analysis of theoretical and regulatory sources, interpretation of legal acts, judicial and arbitration practice).The main results and scope of their application. The current procedure for the provision and payment of utilities is based on the concept of "performer of utilities", which are the management organizations, homeowners' associations, housing cooperatives. The performer of utilities enters into a contract with utilities provider. These utilities are acquired by the contractor at the border of its operational responsibility (on the border of an apartment building), then this resource is already provided as a utility service to final users – tenants and owners of premises in an apartment building. Consumers pay for utility services to the contractor of utilities, and he, in turn, transfers the received payments to the utilities provider (resource supplying organization). Such a scheme of contractual relations leads to problems, including the following: the performers do not enter into contracts with the utilities providers (resource-supplying organizations), thereby trying to exclude their responsibility for the quality of services; do not pay fully or partially for the supplied utility resource. In this regard, the legislation has been amended to allow direct contracts between consumers of public services and resource organizations and, accordingly, directly pay for utilities.Conclusions. Direct contracts between consumers and utilities providers are more convenient for utilities providers than for consumers in the scope of responsibility for the poor quality of utilities.

Digit frequencies and self-affine sets with non-empty interior

In this paper we study digit frequencies in the setting of expansions in non-integer bases, and self-affine sets with non-empty interior. Within expansions in non-integer bases we show that if $\unicode[STIX]{x1D6FD}\in (1,1.787\ldots )$ then every $x\in (0,1/(\unicode[STIX]{x1D6FD}-1))$ has a simply normal $\unicode[STIX]{x1D6FD}$-expansion. We also prove that if $\unicode[STIX]{x1D6FD}\in (1,(1+\sqrt{5})/2)$ then every $x\in (0,1/(\unicode[STIX]{x1D6FD}-1))$ has a $\unicode[STIX]{x1D6FD}$-expansion for which the digit frequency does not exist, and a $\unicode[STIX]{x1D6FD}$-expansion with limiting frequency of zeros $p$, where $p$ is any real number sufficiently close to $1/2$. For a class of planar self-affine sets we show that if the horizontal contraction lies in a certain parameter space and the vertical contractions are sufficiently close to $1$, then every non-trivial vertical fibre contains an interval. Our approach lends itself to explicit calculation and gives rise to new examples of self-affine sets with non-empty interior. One particular strength of our approach is that it allows for different rates of contraction in the vertical direction.

Hypoactivity of rat detrusor muscle in a model of cystitis: exacerbation by non-selective COX inhibitors and amelioration by a selective DP1 receptor antagonist.

Various studies have confirmed that prostaglandins (PG) alter the bladder motor activity and micturition reflex in both human and animals. However, no sufficient data is reported about the effect of cyclooxygenase (COX) inhibitors neither in normal bladder physiology nor in pathological conditions. This study aims to compare the potential effects of some COX inhibitors with varying COX-1/COX-2 selectivities (indomethacin, ketoprofen, and diclofenac) with that of the selective COX-2 inhibitor (DFU) on bladder function. The role played by some PGs and their receptors in controlling detrusor muscle function in normal condition and in cystitis is also studied. Organ bath experiments were performed using isolated rat detrusor muscle. Direct and neurogenic contractions were induced using ACh and electric stimulation (EFS), respectively. A model of hemorrhagic cystitis was induced by single injection of cyclophosphamide (300mg/kg) in rats, and confirmed by histophathological examination. Results are expressed as mean ± SEM of 5-9 rats. Alprostadil and iloprost (1 nM- 10 µM) concentration-dependently potentiated ACh (100μM)- and EFS (4Hz)-induced contraction, with maximum potentiation of 40.01 ± 5.29 and 27.59 ± 6.64%, respectively, in case of ACh contractions. In contrast, ONO-AE1-259 (selective EP2 agonist, 1nM-10μM) inhibited muscle contraction. SC51322 (EP1-antagonist, 10μM) and RO1138452 (IP antagonist, 10μM) inhibited both direct and neurogenic responses. Hemorrhagic cystitis reduced both ACh and EFS responses as well as the potentiatory effect of iloprost and the inhibitory effect of RO1138452 on ACh contractions. ONO-AE3-237 (DP1 antagonist, 1μM) significantly potentiated contractions in cystitis but showed no effect in normal bladder. A significant inhibition of contractile response was observed in presence of indomethacin, ketoprofen, and diclofenac at all tested concentrations (20, 50, and 100μM). Highest effect was induced by diclofenac. The effect of these COX inhibitors on EFS contractions was intensified in case of cystitis, indomethacin being the most potent. Atropine (1nM) significantly reduced indomethacin effect on ACh contraction only in normal rats. On the other hand, DFU (10-6M) significantly potentiated the contractile effect of ACh in case of cystitis although it showed no effect in normal rats. EP1 receptors seem to play an important role in rat bladder contractility. DP1 receptors as COX-2, on the other hand, gain an important role only in case of cystitis. The use of non-selective COX inhibitors in cystitis may be associated with bladder hypoactivity; selective COX-2 inhibitors may be a safer option.

PHP54 - DIRECTIVE 2004/18/EC: IMPLICATIONS FOR PUBLIC MEDICINE PROCUREMENT IN EUROPE

Directive 2004/18/EC provides a framework to any “public contract concluded in one of the EU Member State on behalf of the State, regional or local authorities […]”. This applies to medicines purchased by public hospitals. The research aim is to identify and compare the impact of the directive on procurement in European countries. The Directive 2004/18/EC, national European guidelines on public procurement were reviewed in addition to secondary research to identify any differences in the application of the directive. Procurement models and current level of implementation of the directive were then compared based on past vs future processes to assess any direct impact on the medicines purchase. The research findings were used to develop a typology of the various procurement models as well as to establish any modification in payers’ behaviour regarding medicines purchase. Although the EU directive applies to all European members, differences have been highlighted in countries based on a private vs public national insurance system. Fourteen years after its ratification, countries with less interest in the directive still do not use it, e.g. Italy where a more value-based contract model is used at the national level by AIFA. In countries where fully applied, e.g. Belgium, a shift between direct contracts with manufacturers towards a more transparent and clear tender process is happening. Countries governed by a more private health model, e.g. Netherlands and Germany are less impacted by the introduction of the Directive. Three different models of applications were identified across European countries. Each model impacts the procurement of medicines by influencing payers behaviour, influencing the flexibility for Managed Entry Agreements and modifying the procurement processes.