Enhancing Scientific Support for the Stockholm Convention's Implementation: An Analysis of Policy Needs for Scientific Evidence.

The Stockholm Convention is key to addressing the global threats of persistent organic pollutants (POPs) to humanity and the environment. It has been successful in identifying new POPs, but its national implementation remains challenging, particularly by low- and middle-income Parties. Concerted action is needed to assist Parties in implementing the Convention's obligations. This analysis aims to identify and recommend research and scientific support needed for timely implementation of the Convention. We aim this analysis at scientists and experts from a variety of natural and social sciences and from all sectors (academia, civil society, industry, and government institutions), as well as research funding agencies. Further, we provide practical guidance to scientists and experts to promote the visibility and accessibility of their work for the Convention's implementation, followed by recommendations for sustaining scientific support to the Convention. This study is the first of a series on analyzing policy needs for scientific evidence under global governance on chemicals and waste.

Outcome, Use of Resources and Their Relationship in the Treatment of AMI, Stroke and Hip Fracture at European Hospitals.

The aim of the present study was to compare the quality (survival), use of resources and their relationship in the treatment of three major conditions (acute myocardial infarction (AMI), stroke and hip fracture), in hospitals in five European countries (Finland, Hungary, Italy, Norway and Sweden). The comparison of quality and use of resources was based on hospital-level random effects models estimated from patient-level data. After examining quality and use of resources separately, we analysed whether a cost-quality trade-off existed between the hospitals. Our results showed notable differences between hospitals and countries in both survival and use of resources. Some evidence would support increasing the horizontal integration: higher degrees of concentration of regional AMI care were associated with lower use of resources. A positive relation between cost and quality in the care of AMI patients existed in Hungary and Finland. In the care of stroke and hip fracture, we found no evidence of a cost-quality trade-off. Thus, the cost-quality association was inconsistent and prevailed for certain treatments or patient groups, but not in all countries.

Individual and Regional-level Factors Contributing to Variation in Length of Stay After Cerebral Infarction in Six European Countries.

Using patient-level data for cerebral infarction cases in 2007, gathered from Finland, Hungary, Italy, the Netherlands, Scotland and Sweden, we studied the variation in risk-adjusted length of stay (LoS) of acute hospital care and 1-year mortality, both within and between countries. In addition, we analysed the variance of LoS and associations of selected regional-level factors with LoS and 1-year mortality after cerebral infarction. The data show that LoS distributions are surprisingly different across countries and that there is significant deviation in the risk-adjusted regional-level LoS in all of the countries studied. We used negative binomial regression to model the individual-level LoS, and random intercept models and ordinary least squares regression for the regional-level analysis of risk-adjusted LoS, variance of LoS, 1-year risk-adjusted mortality and crude mortality for a period of 31-365 days. The observed variations between regions and countries in both LoS and mortality were not fully explained by either patient-level or regional-level factors. The results indicate that there may exist potential for efficiency gains in acute hospital care of cerebral infarction and that healthcare managers could learn from best practices.

Willingness and ability to pay for unexpected dental expenses by Finnish adults.

BACKGROUND: Since 2002, adults have been able to choose oral health care services in the public sector or in the private sector in Finland. Though various subsidies for care exist in both sectors, the Public Dental Service (PDS) is a cheaper option for the patient but, on the other hand, there are no waiting lists for private care. The aim of this study was to assess middle-aged adults' use of dental services, willingness to pay (WTP) and ability to pay (ATP) for unexpected, urgent dental treatment. METHODS: Postal questionnaires on use of dental services were sent to a random sample of 1500 47-59 year old adults living in three large municipalities in the Helsinki region. The initial response rate was 65.8%. Two hypothetical scenarios were presented: "What would be the highest price you would be prepared to pay to have a lost filling replaced immediately, or, at the latest, the day after losing the filling?" and " How much could you pay for unexpected dental expenses at two weeks notice, if you suddenly needed more comprehensive treatment?" Logistic regression analysis was used to analyse factors related to WTP and ATP. RESULTS: Most respondents (89.6%) had visited a dentist recently and a majority (76.1%) had used private services. For immediate replacement of a lost filling, almost all respondents (93.2%) were willing to pay the lower price charged in the PDS and 46.2% were willing to pay the private fee. High income and no subjective need for dental treatment were positively associated with the probability of paying a higher price. Most respondents (93.0%) were able to pay a low fee, EUR 50 and almost half (41.6%) at least EUR 300 for unexpected treatment at short notice. High income and male sex were associated with high ATP. CONCLUSION: There was a strong and statistically significant relationship between income and WTP and ATP for urgent dental care, indicating that access to publicly provided services improved equity for persons with low income.

Estimating firm digitalization: A method for disaggregating sector-level digital intensity to firm-level.

The digital transformation of firms plays an increasingly important role in the economy and society. However, limited access to data on firm-level digital intensity is an impediment to advancement of multiple research projects concerned with firm digitalization. To alleviate this challenge, this paper proposes a method for estimating firm-level digital intensity based on other more readily available firm-level data and reference data on digitalization, which is available on sector-level. The proposed method utilizes firm-level revenue breakdown by sector to estimate sector revenue-weighted digital intensity scores, which lead to classification of firms into low, medium and high digital intensity groups. The output from the proposed method can be directly used in research concerned with firm digitalization and investigating this multifaceted phenomenon. Results from the application of the proposed method to an illustrative sample of large US and non-US firms (2000 observations in total) indicate that firm-level digital intensity can be efficiently estimated for large samples using data commonly available to researchers. The key differences between the proposed method and alternative methods are:•Recognition of the fact that firms might participate in more than one sector or industry, which partially explains within-sector heterogeneity in firm-level digital intensity. We found that 67.8% of large US firms and 78.6% of large non-US firms were engaged in more than one industry.•Use of reference sector-level digital intensity scores, which allows for rapid update, application across geographies and time, as well as parallel calculation of multiple digital intensity scores for each reference data. Furthermore, use of reference data enables supplementation of firm-level data on digitalization.•Replicability of the method and reproducibility of the results through inclusion of the source code and availability of data through research and commercial databases.

Data Sharing in Pharmaceutical Supply Chains - Case European Medicines Verification System.

We study the perceived value derived from data sharing activities by the representatives of a Nordic pharmaceutical company in the introduction of the European Medicines Verification System (EMVS). The system is an end-to-end verification protocol that would potentially enable the pharmaceutical companies to access the sales-point data from within the system, while maintaining the control of their own data. The benefits of the system are most notably in developing data sharing with the wholesalers and end-customers. Development of data sharing practices might enable more transparent logistics, and more targeted services and products.

Commercial Adoption of AI in the Healthcare Sector: An Exploratory Analysis of S&P500 Companies.

The use of Artificial Intelligence (AI) technologies within the healthcare sector is growing. However, there are differences in the speed of commercial adoption of AI across sub-sectors. We employ a dataset including news mentions and executive communications of all S&P500 Health Care Index companies to explore these differences. Pharmaceutical and medicine manufacturing companies had the earliest AI-linked news presence, yet they appeared to be among the slowest commercial implementers of AI. Ambulatory health care services and hospitals, as well as insurance carriers, received media coverage later, but were the quickest to take AI into commercial use. From the theory perspective our results indicate that the classical innovation diffusion theory might not fully explain these differences.

The effects of d-amphetamine on extrastriatal dopamine D2/D3 receptors: a randomized, double-blind, placebo-controlled PET study with [11C]FLB 457 in healthy subjects.

PURPOSE: The dopamine D(2)/D(3) receptor ligand [(11)C]FLB 457 and PET enable quantification of low-density extrastriatal D(2)/D(3) receptors, but it is uncertain whether [(11)C]FLB 457 can be used for measuring extrastriatal dopamine release. METHODS: We studied the effects of d-amphetamine (0.3 mg/kg i.v.) on extrastriatal [(11)C]FLB 457 binding potential (BP(ND)) in a randomized, double-blind, placebo-controlled study including 24 healthy volunteers. RESULTS: The effects of d-amphetamine on [(11)C]FLB 457 BP(ND) and distribution volume (V(T)) in the frontal cortex were not different from those of placebo. Small decreases in [(11)C]FLB 457 BP(ND) were observed only in the posterior cingulate and hippocampus. The regional changes in [(11)C]FLB 457 BP(ND) did not correlate with d-amphetamine-induced changes in subjective ratings of euphoria. CONCLUSION: This placebo-controlled study showed that d-amphetamine does not induce marked changes in measures of extrastriatal dopamine D(2)/D(3) receptor binding. Our results indicate that [(11)C]FLB 457 PET is not a useful method for measuring extrastriatal dopamine release in humans.

Factors Affecting Venture Funding of Healthcare AI Companies.

Venture Capital (VC) funding raised by companies producing Artificial Intelligence (AI) or Machine Learning (ML) solutions is on the rise and a driver of technology development. In healthcare, VC funding is distributed unevenly and certain technologies have attracted significantly more funding than others have. We analyzed a database of 106 Healthcare AI companies collected from open online sources to understand factors affecting the VC funding of AI companies operating in different areas of healthcare. The results suggest that there is a significant connection between higher funding and having research organizations or pharmaceutical companies as the customer of the product or service. In addition, focusing on AI solutions that are applied to direct patient care delivery is associated with lower funding. We discuss the implications of our findings for public health technology funding institutions.

Sub-chronic nandrolone treatment modifies neurochemical and behavioral effects of amphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in rats.

Misuse of anabolic-androgenic steroids (AASs) is increasing, and appears to have much in common with the use of substances known to induce drug dependence. Moreover, persons who abuse AASs also tend to abuse other psychotropic drugs such as amphetamine or 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy"). The aim of this study was to investigate whether nandrolone (5 x 5 or 5 x 20 mg/kg) pre-exposure modulates the acute neurochemical and behavioral effects of amphetamine (1mg/kg) and MDMA (5 mg/kg) in rats. Dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were measured from samples collected from the nucleus accumbens (NAc) by in vivo microdialysis. The behavior of the animals was recorded on videotapes, from which it was later rated. Our results demonstrate that sub-chronic treatments with supraphysiological doses of nandrolone attenuate dose-dependently the increase in extracellular DA concentration evoked by amphetamine or MDMA. The lower dose of nandrolone attenuated MDMA-induced increase in 5-HT-levels, while the higher dose potentiated it. Analysis of the behavioral data suggests that effects of the amphetamine and MDMA are dose-dependently attenuated by AAS-treatment, paralleling DA results. In conclusion, the results of this study show that AAS-pre-treatment is able to modulate the reward-related neurochemical and behavioral effects of amphetamine and MDMA.

Production flow analysis: a tool for designing a lean hospital.

Production flow analysis (PFA) was used in the planning process for a new acute care hospital. The PFA demonstrated that functional organisation--for example, with centralised medical imaging-- generates a lot of back and forth patient transfers between functional units. This to-and-fro patient flow increases lead times of care processes and also exposes the patients to unnecessary complications. PFA produced an ideal patient flow model and layout model for the acute care hospital. Thus, PFA revealed information for use in proximity ranking of different units of the hospital; the planning team then decided which units should be placed next to each other. Medical imaging should be essentially ubiquitous, to achieve simple, high-velocity patient flow. Thus, a modern decentralized layout model for medical imaging was planned. Furthermore, PFA enables optimizing transfer routes for patients and also, e.g., lift capacity in the hospital.

Correction: Mortality and Length of Stay of Very Low Birth Weight and Very Preterm Infants: A EuroHOPE Study.

[This corrects the article DOI: 10.1371/journal.pone.0131685.].

Rewarding properties of 1-benzylpiperazine, a new drug of abuse, in rats.

1-Benzylpiperazine (also known as 'Legal X', 'Legal E', or 'A2') is a psychoactive compound increasingly encountered on the clandestine market. Previous experimental data suggest that the compound possesses addictive properties. In the present study, we used the conditioned place preference method in the rat to test whether 1-benzylpiperazine possesses rewarding properties. Furthermore, the mechanisms of the 1-benzylpiperazine reward were investigated using selected dopamine and serotonin receptor antagonists. 1-Benzylpiperazine (1.25, 5, and 20 mg/kg) induced dose-dependently place preference. This place preference was attenuated by the antagonists SCH23390 (0.2 mg/kg; dopamine D1-like receptors) and MDL72222 (1.0 mg/kg; serotonin3 receptors), but not by raclopride (0.8 mg/kg; dopamine D2-like receptors) or ketanserin (2 mg/kg; preferentially serotonin2 receptors). Our results show that 1-benzylpiperazine possesses rewarding properties in the rat, which suggests the compound to be susceptible to human abuse. The brain dopaminergic and serotonergic systems appear to be involved in the 1-benzylpiperazine reward.

The effect of sub-chronic nandrolone decanoate treatment on dopaminergic and serotonergic neuronal systems in the brains of rats.

Anabolic-androgenic steroids (AASs) are widely abused by adolescents, although persistent AAS use can cause several adverse physical and mental effects, including drug dependence. The first aim of the present study was to study the action of nandrolone decanoate on dopaminergic and serotonergic activities in the brains of rats. In order to evaluate the anabolic or toxic effects of the dosing regimens used, selected peripheral effects were monitored as well. Male Wistar rats were treated for 2 weeks. Injections containing nandrolone (5 and 20 mg/kg, i.m.) or vehicle were given once daily, 5 days a week. The levels of dopamine (DA), 5-hydroxytryptamine (5-HT) and their metabolites were assayed from dissected brain regions 3 days after the last injection. Blood was collected for chemical assays before, after 1 week treatment and at decapitation. Both doses of nandrolone significantly increased the levels of 3,4-dihydroxyphenylacetic acid (DOPAC), a metabolite of DA in the cerebral cortex, and the higher dose of nandrolone increased the concentrations of 5-HT in the cerebral cortex compared with the vehicle. In addition, after nandrolone treatment, the levels of hemoglobin and erythrocytes increased, and reticulocyte levels decreased. The results suggest that nandrolone at supraphysiological doses, high enough to induce erythropoiesis, induces changes in the dopaminergic and serotonergic neuronal system in the brains of rats. These phenomena may account to some of the observed central stimulatory properties that have been reported following AAS abuse.

Rewarding properties of the stereoisomers of 4-methylaminorex: involvement of the dopamine system.

4-Methylaminorex is a potential psychostimulant drug of abuse that exists as four stereoisomers: cis-4R,5S, cis-4S,5R, trans-4S,5S, and trans-4R,5R. The racemic mixture of the cis-isomers has been encountered in illicit samples, but previous animal studies suggest that also the trans-isomers could have similar stimulant-like properties. We tested whether the stereoisomers possess rewarding properties and compared their potency using the conditioned place preference method in rats. Furthermore, the involvement of the brain dopaminergic system in the 4-methylaminorex reward was tested with the dopamine D1- and D2-receptor antagonists SCH 23390 and raclopride administered systemically, or with the neurotoxin 6-hydroxydopamine injected into the nucleus accumbens. All the four isomers induced place preference, with no apparent differences in their potency. SCH 23990 and raclopride attenuated 4-methylaminorex-induced increase in place preference, and 6-hydroxydopamine also tended to be efficacious. These findings indicate that all the four stereoisomers of 4-methylaminorex possess rewarding properties and thus abuse potential; the trans-isomers are at least as potent as the cis-isomers. Furthermore, the brain dopaminergic system appears to be involved in the 4-methylaminorex-reward.

Mortality and Length of Stay of Very Low Birth Weight and Very Preterm Infants: A EuroHOPE Study.

The objective of this paper was to compare health outcomes and hospital care use of very low birth weight (VLBW), and very preterm (VLGA) infants in seven European countries. Analysis was performed on linkable patient-level registry data from seven European countries between 2006 and 2008 (Finland, Hungary, Italy (the Province of Rome), the Netherlands, Norway, Scotland, and Sweden). Mortality and length of stay (LoS) were adjusted for differences in gestational age (GA), sex, intrauterine growth, Apgar score at five minutes, parity and multiple births. The analysis included 16,087 infants. Both the 30-day and one-year adjusted mortality rates were lowest in the Nordic countries (Finland, Sweden and Norway) and Scotland and highest in Hungary and the Netherlands. For survivors, the adjusted average LoS during the first year of life ranged from 56 days in the Netherlands and Scotland to 81 days in Hungary. There were large differences between European countries in mortality rates and LoS in VLBW and VLGA infants. Substantial data linkage problems were observed in most countries due to inadequate identification procedures at birth, which limit data validity and should be addressed by policy makers across Europe.

Analgesic effects of dextromethorphan and morphine in patients with chronic pain.

N-methyl-aspartate (NMDA) receptor antagonists have been shown to improve opioid analgesia in the animal model. The cough suppressant dextromethorphan is a clinically available NMDA-receptor antagonist. In this randomised, double-blind, placebo-controlled study 20 patients with chronic pain of several years duration were given 100 mg of oral dextromethorphan or matching placebo 4 h prior to an intravenous infusion of morphine 15 mg. Pain intensity and adverse effects were assessed at 0, 4, 5 and 7 h. Dextromethorphan had no effect on morphine analgesia: the mean (+/-SEM) visual analogue scores for pain relief (VAS, 0-100 mm) at the end of the morphine infusion were 38 (+/-6) for dextromethorphan+morphine and 38 (+/-7) for placebo+morphine. VAS scores for pain intensity were comparable both at rest and at movement at all time points. The most common adverse effects reported were dizziness, nausea and sedation. There were no significant differences in either the incidence or severity of adverse effects. In conclusion, oral dextromethorphan 100 mg had no effect on pain relief by intravenous morphine 15 mg in patients with chronic pain.

5-HT3 receptor antagonist MDL 72222 attenuates cocaine- and mazindol-, but not methylphenidate-induced neurochemical and behavioral effects in the rat.

RATIONALE: It has previously been demonstrated that the 5-HT(3) receptors located in the mesolimbic brain areas are able to modulate the dopaminergic effects of various abused drugs, including cocaine (COC). OBJECTIVES: The present experiments investigated the role of 5-HT(3) receptors in the actions of selected monoamine uptake inhibitors. METHODS: The ability of the 5-HT(3) receptor antagonist MDL 72222 (MDL; 0.1 and 1.0 mg/kg) to modify the neurochemical and behavioral changes induced by COC (20 mg/kg), mazindol (MAZ; 10 mg/kg), and methylphenidate (MP; 5.0 or 10, and 20 mg/kg) was assessed with an in vivo microdialysis technique, a conditioned place preference method, and motor activity measurements. RESULTS: MDL robustly attenuated the elevation of extracellular dopamine levels in the nucleus accumbens, acquisition of place preference, and motor activity induced by COC and MAZ, but not those induced by MP, the only drug with no significant effect on 5-HT. In contrast, expression of COC-induced place preference was not attenuated by MDL. CONCLUSIONS: These results show that COC- and MAZ-induced reward-related neurochemical and behavioral effects, preferentially those implicated in development of conditioned reward, are modified by the 5-HT(3) blockade. In contrast to COC and MAZ, the changes induced by MP, which has less effect on the serotonergic system, remain unchanged. Thus it appears that involvement of a serotonergic component in the mechanism of action of a drug could be a prerequisite for effective antagonism by 5-HT(3) receptor blockers.

Steroid use and long-term health risks in former athletes.

This article focuses on anabolic steroid adverse effects on the cardiovascular system and mental health issues as well as the possible increase in the incidence of neoplasms in anabolic steroid users. On the basis of findings in the literature, the authors consider these three issues as the most significant concerning morbidity and mortality among anabolic steroid users. A study by Pärssinen et al. (2000) has shown an increased incidence of premature mortality among power lifters. Anabolic steroids and other concomitantly used drugs are the probable cause of this increased mortality, as power training itself does not increase health risks and all types of physical activity promote health.