bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Environmental Regulations on Trade in the Main EU Countries: Conflict or Synergy?
Authors: De Santis Roberta 
Published: April 2012

AbstractIn an increasingly integrated world with declining trade barriers, environmental regulations can have a decisive role in shaping countries’ comparative advantages. The conventional wisdom about environmental protection is that it comes at an additional cost on firms imposed by the government, which may erode their global competitiveness. However, this paradigm has been challenged by some analysts. In particular, Porter and van der Linde argue that pollution is often associated with a waste of resources and that more stringent environmental policies can stimulate innovations that may overcompensate for the costs of complying with these policies. This is known as the Porter hypothesis. While there is a broad empirical literature on the impact of trade on environment, the empirical literature on the impact of environmental regulations on trade flows is relatively scarce, very heterogeneous and presents mixed results. The innovative feature of this paper is its attempts to estimate, in a gravity setting, augmented with a proxi of environmental stringency, the impact of three major multilateral environmental agreements (MEAs) on 15 EU countries’ bilateral exports. According to our estimates, in the period 1988–2008, to be member of MEAs had a positive average impact on EU‐15 bilateral exports. This evidence can be partly explained by a possible trade diversion effect with respect to countries that did not sign MEAs and a corresponding trade creation effect among members of the environmental agreements. Furthermore, evidence coming from interaction effects estimates seems to show that for exporting countries, having signed the United Nations Framework Convention on Climate Change and the Montreal agreements partly mitigates (by the amount of the estimated coefficient) the negative impact of having a relatively more stringent environmental regulation on bilateral trade. This result could have important policy implications for the future international trade–environmental negotiations.
Patient‐reported convenience of once‐daily versus three‐times‐daily dosing during long‐term studies of pramipexole in early and advanced Parkinson’s disease
Authors: Schapira A. H. V. , Barone P. , Hauser R. A. , Mizuno Y. , Rascol O. , Busse M. , Debieuvre C. , Fraessdorf M. , Poewe W. ,   for the Pramipexole ER Studies Group
Published: April 2012

Background and purpose:  In chronic diseases including Parkinson’s disease (PD), complex pharmacotherapy dosing schedules are reported to reduce adherence, perhaps leading to less‐effective symptom control and, in PD, more erratic stimulation of dopamine receptors. However, blinded clinical‐trial designs preclude direct comparisons of adherence to various schedules.Methods:  In two double‐blind (DB) studies of early PD and one of advanced PD, subjects received three‐times‐daily (t.i.d.) pramipexole or placebo. In open‐label (OL) extensions, subjects took extended‐release, once‐daily (q.d.) pramipexole. At 24 or 32 OL weeks, q.d. versus t.i.d. dosing preference was surveyed by questionnaire.Results:  Of 590 DB‐trial completers with early PD, 511 entered the OL extension. Of 374 survey respondents, 94.4% preferred q.d. dosing (72.2% of them found it ‘very much more convenient’ and 27.8%‘more convenient’), 2.7% preferred t.i.d., and 2.9% chose ‘no difference’. Of 465 DB‐trial completers with advanced PD, 391 entered its OL extension. Of 334 survey respondents, 88.9% preferred q.d. dosing (59.9% of them found it ‘very much more convenient’ and 40.1%‘more convenient’), 5.7% preferred t.i.d., and 5.4% chose ‘no difference’. Results excluding DB‐placebo recipients were highly similar.Conclusions:  In this first direct comparison of patient preference for q.d. versus t.i.d. dopamine‐agonist dosing, patients with early or advanced PD had a strong preference for q.d. rather than t.i.d. pramipexole. The high proportion of advanced‐PD patients declaring this preference indicates that it does not depend on whether a patient is taking concomitant PD medications dosed more frequently than q.d.
Trauma and amyotrophic lateral sclerosis: a case–control study from a population‐based registry
Authors: Pupillo E. , Messina P. , Logroscino G. , Zoccolella S. , Chiò A. , Calvo A. , Corbo M. , Lunetta C. , Micheli A. , Millul A. , Vitelli E. , Beghi E. ,   EURALS Consortium
Published: April 2012

Background and purposePublished reports on the association between amyotrophic lateral sclerosis (ALS) and trauma are controversial suggesting the need for a new case–control study done in a large population.MethodsA case–control study was undertaken in Italy to assess this association. Cases were patients with newly diagnosed ALS from four population‐based registries. For each case, two hospital controls were selected, matched for age, sex, and province of residence, one with a neurological (non‐degenerative) disease and one with a non‐neurological disease (other than orthopedic or surgical). Traumatic events (defined as accidental events causing injuries requiring medical care) were recorded with details on type, site, timing, severity, and complications. The risks were assessed as odds ratios (ORs) with 95% confidence intervals (CI), crude and adjusted for age, sex, education, interviewee (patient or surrogate), physical activity, smoking, alcohol, and coffee.ResultsThe study population comprised 377 patients in each of the three groups. One or more traumatic events were reported by 225 cases (59.7%), 191 neurological controls (50.7%), and 179 non‐neurological controls (47.5%) (P < 0.01) (OR 1.63; 95% CI 1.25–2.14) (P < 0.01). The ORs were 3.07 (95% CI 1.86–5.05) for patients reporting 3+ traumatic events and 2.44 (95% CI 1.36–4.40) for severe traumatic events. The ORs remained significant when the analysis was limited to events that occurred 5+ and 10+ years before ALS onset, to incident ALS, and direct informant.ConclusionAntecedent trauma, repeated trauma, and severe trauma may be risk factors for ALS.
Gender‐Specific Migration from Eastern to Western Germany: Where Have All the Young Women Gone?
Authors: Kröhnert Steffen , Vollmer Sebastian 
Published: April 2012

AbstractWith the fall of the Berlin Wall in 1989, open migration from East to West Germany became possible. Between 1989 and 2007, roughly 10 per cent of the East’s population at the time of reunification migrated from east to west. The emigrants were predominantly young and female. This selective migration pattern led to a tremendous deficit of females in the 18–29 year old age group in eastern Germany. Overall, the sex ratio in that age group is as low as 89 females per 100 males in the east. In some rural counties, the sex ratio is 80 females per 100 males. We find that excess female emigration at the county level is associated with gender disparities in educational attainment that favour women, a labour market structure that favours men and the lower availability of potential partners with similar levels of education in eastern Germany.
Innocent Threats and the Moral Problem of Carnivorous Animals
Authors: EBERT RAINER , MACHAN TIBOR R. 
Published: April 2012

abstractThe existence of predatory animals is a problem in animal ethics that is often not taken as seriously as it should be. We show that it reveals a weakness in Tom Regan's theory of animal rights that also becomes apparent in his treatment of innocent human threats. We show that there are cases in which Regan's justice‐prevails‐approach to morality implies a duty not to assist the jeopardized, contrary to his own moral beliefs. While a modified account of animal rights that recognizes the moral patient as a kind of entity that can violate moral rights avoids this counterintuitive conclusion, it makes non‐human predation a rights issue that morally ought to be subjected to human regulation. Jennifer Everett, Lori Gruen and other animal advocates base their treatment of predation in part on Regan's theory and run into similar problems, demonstrating the need to radically rethink the foundations of the animal rights movement. We suggest to those who, like us, find it less plausible to introduce morality to the wild than to reject the concept of rights that makes this move necessary to read our criticism either as a modus tollens argument and reject non‐human animal rights altogether or as motivating a libertarian‐ish theory of animal rights.
Development and embryonic staging in non‐model organisms: the case of an afrotherian mammal
Authors: Werneburg Ingmar , Tzika Athanasia C. , Hautier Lionel , Asher Robert J. , Milinkovitch Michel C. , Sánchez‐Villagra Marcelo R. 
Published: April 2012

AbstractStudies of evolutionary developmental biology commonly use ‘model organisms’ such as fruit flies or mice, and questions are often functional or epigenetic. Phylogenetic investigations, in contrast, typically use species that are less common and mostly deal with broad scale analyses in the tree of life. However, important evolutionary transformations have taken place at all taxonomic levels, resulting in such diverse forms as elephants and shrews. To understand the mechanisms underlying morphological diversification, broader sampling and comparative approaches are paramount. Using a simple, standardized protocol, we describe for the first time the development of soft tissues and some parts of the skeleton, using μCT‐imaging of developmental series of Echinops telfairi and Tenrec ecaudatus, two tenrecid afrotherian mammals. The developmental timing of soft tissue and skeletal characters described for the tenrecids is briefly compared with that of other mammals, including mouse, echidna, and the opossum. We found relatively few heterochronic differences in development in the armadillo vs. tenrec, consistent with a close relationship of Xenarthra and Afrotheria. Ossification in T. ecaudatus continues well into the second half of overall gestation, resembling the pattern seen in other small mammals and differing markedly from the advanced state of ossification evident early in the gestation of elephants, sheep, and humans.
Clinical decision‐making process for early nonspecific signs of infection in institutionalised elderly persons: experience of nursing assistants
Authors: Sund‐Levander Märtha , Tingström Pia 
Published: April 2012

Scand J Caring Sci; 2013; 27; 27–35

Clinical decision‐making process for early nonspecific signs of infection in institutionalised elderly persons: experience of nursing assistants
Aim:  To illuminate nursing assistant’s experiences of the clinical decision‐making process when they suspect that a resident has an infection and how their process relates to other professions.Background:  The assessment of possible infection in elderly individuals is difficult and contributes to a delayed diagnosis and treatment, worsening the goal of good care. Recently we explored that nursing assistants have a keen observational ability to detect early signs and symptoms that might help to confirm suspected infections early on. To our knowledge there are no published papers exploring how nursing assistants take part in the clinical decision‐making process.Design:  Explorative, qualitative study.Setting:  Community care for elderly people.Participants:  Twenty‐one nursing assistants, 22–61 years.Methods:  Focus groups with verbatim transcription. The interviews were subjected to qualitative content analysis for manifest and latent content with no preconceived categories.Findings:  The findings are described as a decision‐making model consisting of assessing why a resident feels unwell, divided into recognition and formulation and strategies for gathering and evaluating information, influenced by personal experiences and preconceptions and external support system and, secondly, as taking action, consisting of reason for choice of action and action, influenced by feedback from the nurse and physician.Conclusion:  Nursing assistant’s assessment is based on knowing the resident, personal experiences and ideas about ageing. Nurses and physician’s response to the nursing assistant’s observations had a great impact on the latter’s further action. A true inter‐professional partnership in the clinical decision‐making process would enhance the possibility to detect suspected infection early on, and thereby minimize the risk of delayed diagnosis and treatment and hence unnecessary suffering for the individual.Relevance to clinical practice:  In order to improve the clinical evaluation of the individual, and thereby optimise patient safety, it is important to involve nursing assistants in the decision‐making process.
The α7 nicotinic ACh receptor agonist compound B and positive allosteric modulator PNU‐120596 both alleviate inflammatory hyperalgesia and cytokine release in the rat
Authors: Munro G , Hansen RR , Erichsen HK , Timmermann DB , Christensen JK , Hansen HH 
Published: April 2012

BACKGROUND AND PURPOSE Agonists selective for the α7 nicotinic acetylcholine (nACh) receptor produce anti‐hyperalgesic effects in rodent models of inflammatory pain, via direct actions on spinal pain circuits and possibly via attenuated release of peripheral pro‐inflammatory mediators. Increasingly, allosteric modulation of ligand‐gated receptors is recognized as a potential strategy to obtain desired efficacy in the absence of the putative adverse effects associated with agonist activation.EXPERIMENTAL APPROACH We compared the anti‐hyperalgesic and anti‐inflammatory effects of the α7 nACh receptor agonist compound B with the positive allosteric modulator (PAM) PNU‐120596 and the standard non‐steroidal anti‐inflammatory drug (NSAID), diclofenac, in rats with hind paw inflammation induced by either formalin, carrageenan or complete Freund's adjuvant (CFA).KEY RESULTS When administered before carrageenan, both diclofenac (30 mg·kg−1) and PNU‐120596 (30 mg·kg−1) significantly reduced mechanical hyperalgesia and weight‐bearing deficits for up to 4 h. Compound B (30 mg·kg−1) also attenuated both measures of pain‐like behaviour, albeit less robustly. Whereas compound B and PNU‐120596 attenuated the carrageenan‐induced increase in levels of TNF‐α and IL‐6 within the hind paw oedema, diclofenac only attenuated IL‐6 levels. Established mechanical hyperalgesia induced by carrageenan or CFA was also partially reversed by compound B and PNU‐120596. However, diclofenac was considerably more efficacious. Formalin‐induced nocifensive behaviours were only reversed by compound B, albeit at doses which disrupted motor performance.CONCLUSIONS AND IMPLICATIONS α7 nACh receptor PAMs could prove to be useful in the treatment of inflammatory pain conditions, which respond poorly to NSAIDs or in situations where NSAIDs are contra‐indicated.
Regional‐ and agonist‐dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists
Authors: Broad J , Mukherjee S , Samadi M , Martin JE , Dukes GE , Sanger GJ 
Published: April 2012

BACKGROUND AND PURPOSE Delayed gastric emptying is poorly managed. Motilin agonists are potential treatments but inadequate understanding into how enteric nerve functions are stimulated compromises drug/dose selection. Resolution is hampered by extreme species dependency so methods were developed to study human gastrointestinal neuromuscular activities and the neurobiology of motilin.EXPERIMENTAL APPROACH Protocols to study neuromuscular activities were developed for different regions of human stomach and intestine (71 patients) using circular muscle preparations and electrical field stimulation (EFS) of intrinsic nerves. Other tissues were fixed for immunohistochemistry.KEY RESULTS EFS evoked contractions and/or relaxations via cholinergic and nitrergic neurons, with additional tachykinergic activity in colon; these were consistent after 154 min (longer if stored overnight). Motilin 1–300 nM and the selective motilin agonist GSK962040 0.1–30 µM acted pre‐junctionally to strongly facilitate cholinergic contractions of the antrum (Emax≈ 1000% for motilin), with smaller increases in fundus, duodenum and ileum; high concentrations increased baseline muscle tension in fundus and small intestine. There were minimal effects in the colon. In the antrum, cholinergic facilitation by motilin faded irregularly, even with peptidase inhibitors, whereas facilitation by GSK962040 was long lasting. Motilin receptor immunoreactivity was identified in muscle and myenteric plexus predominantly in the upper gut, co‐expressed with choline acetyltransferase in neurons.CONCLUSIONS AND IMPLICATIONS Motilin and GSK962040 strongly facilitated cholinergic activity in the antrum, with lower activity in fundus and small intestine only. Facilitation by motilin was short lived, consistent with participation in migrating motor complexes. Long‐lasting facilitation by GSK962040 suggests different receptor interactions and potential for clinical evaluation.LINKED ARTICLE This article is commented on by Depoortere, pp. 760–762 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476‐5381.2012.02046.x
Evaluation ofFOXP3expression in canine mammary gland tumours
Authors: Oh S. Y. , Ryu H. H. , Yoo D. Y. , Hwang I. K. , Kweon O. K. , Kim W. H. 
Published: April 2012

AbstractThe expression of the transcription factor forkhead box P3(FOXP3) was examined in 62 canine mammary gland tumours via immunohistochemical analysis and association with the known expression of the oestrogen receptor‐alpha (ERα), progesterone receptor (PR),c‐erbB‐2receptor (HER2/neu), and survival. Positive staining forFOXP3was present in 22.6% of the tumours and was associated with the histological type. Negative staining forFOXP3was associated with positiveERαandPRexpression (P < 0.001). The expression ofFOXP3in canine mammary gland tumours was significantly associated with the disease‐free survival time (P = 0.029). TheFOXP3expression was not an independent prognostic factor in the multivariate analysis, though. The negative expression ofFOXP3in the canine mammary gland tumours was found to be related to histopathologic benignity and a longer survival time in canine mammary gland tumours.
Advanced Interventions for Headache
Authors: Tepper Stewart J. 
Published: April 2012

Many headache patients present when medications fail, are inadequate, are contraindicated, or are not tolerated. These are patients with severe disability. Most have daily headaches, including chronic migraine, trigeminal autonomic cephalalgias, or other primary headaches. This brief review addresses, in broad strokes, some thoughts about alternatives beyond the usual daily oral preventive therapies.Do not proceed to more invasive or elaborate approaches until the big 3 are done: diagnosis is established, onabotulinumtoxinA administered when appropriate, that is, if the patient has chronic migraine, and wean is accomplished if the patient has medication overuse headache. Large numbers of patients are helped without the need for more arcane and unproven treatments by following these initial approaches. Simple nerve blocks can be useful in the initial steps, but more invasive blocks and stimulators are not recommended until the big 3 are completed.Wean of overused medications must be absolute and may require an intravenous bridge over several days, either in an infusion unit or inpatient in a medical model. Wean should be accompanied by establishing onabotulinumtoxinA or daily prevention from the beginning.Consider referral to a structured multidisciplinary headache program. This is for patients who require an interdisciplinary approach and may be day‐hospital or inpatient.Invasive blocks and stimulators may be appropriate, and the latter are currently being studied in controlled studies. The most promise, with the best balance of efficacy vs adverse event prospects, may be occipital nerve stimulators or sphenopalatine ganglion stimulators.
Opioids Should Not Be Used in Migraine
Authors: Tepper Stewart J. 
Published: April 2012

Opioids should not be used for the treatment of migraine. This brief review explores why not. Alternative acute and preventive agents should always be explored.Opioids do not work well clinically in migraine. No randomized controlled study shows pain‐free results with opioids in the treatment of migraine. Saper and colleagues' 5‐year study showed minimal effectiveness, with many contract violations, interfering with the therapeutic alliance.The physiologic consequences of opioid use are adverse, occur quickly, and can be permanent. Decreased gray matter, release of calcitonin gene‐related peptide, dynorphin, and pro‐inflammatory peptides, and activation of excitatory glutamate receptors are all associated with opioid exposure. Opioids are pro‐nociceptive, prevent reversal of migraine central sensitization, and interfere with triptan effectiveness.Opioids precipitate bad clinical outcomes, especially transformation to daily headache. They cause disease progression, comorbidity, and excessive health care consumption. Use of opioids in migraine is pennywise and pound foolish.
Results of a Double‐blind, Placebo‐controlled, Fixed‐dose Assessment of Once‐daily OROS® Hydromorphone ER in Patients with Moderate to Severe Pain Associated with Chronic Osteoarthritis
Authors: Rauck Richard , Rapoport Ronald , Thipphawong John 
Published: April 2012

AbstractObjective:  Opioids are recommended for patients with moderate to severe pain due to osteoarthritis (OA), who do not receive adequate analgesia from nonopioid treatment. The objective of this study was to evaluate the efficacy and safety of OROS hydromorphone extended‐release (ER) compared with placebo in patients with moderate to severe pain associated with OA.Methods:  This was a randomized, placebo‐controlled, double‐blind, fixed‐dose study. Patients received placebo or fixed‐dose OROS hydromorphone ER (8 or 16 mg). The primary efficacy measure was pain intensity score (11‐point Numeric Rating Scale) at Maintenance Week 12, analyzed with baseline observation carried forward (BOCF) imputation for missing data.Results:  This study did not meet the primary efficacy measure using the BOCF imputation. Study discontinuation was high (52%). When analyzed using last observation carried forward (LOCF) imputation, the prespecified alternate method, OROS hydromorphone ER 16 mg provided significantly better analgesia than placebo (P = 0.0009). Treatment was associated with significant improvements in patient global assessment (P = 0.01), the overall Western Ontario and McMaster Osteoarthritis Index (WOMAC) (P = 0.0003), and its subscales: pain (P = 0.0001), stiffness (P = 0.0023), and physical function (P = 0.0006). Gastrointestinal adverse events, such as constipation and nausea, were common among patients receiving OROS hydromorphone ER.Conclusions:  OROS hydromorphone ER failed to achieve statistical significance for the primary endpoint using the prespecified imputation method (BOCF), likely due to the high discontinuation rate associated with the fixed‐dose design. When data were analyzed according to an alternate method of imputation (LOCF), OROS hydromorphone ER demonstrated statistically significant improvements in pain, stiffness, and physical function.