A direct advance on advance directives

Advance directives (ADs), which are also sometimes referred to as 'living wills', are statements made by a person that indicate what treatment she should not be given in the event that she is not competent to consent or refuse at the future moment in question. As such, ADs provide a way for patients to make decisions in advance about what treatments they do not want to receive, without doctors having to find proxy decision-makers or having recourse to the doctrine of necessity. While patients can request particular treatments in an AD, only refusals are binding. This paper will examine whether ADs safeguard the autonomy and best interests of the incompetent patient, and whether legislating for the use of ADs is justified, using the specific context of the legal situation in the United Kingdom to illustrate the debate. The issue of whether the law should permit ADs is itself dependent on the issue of whether ADs are ethically justified; thus we must answer a normative question in order to answer the legislative one. It emerges that ADs suffer from two major problems, one related to autonomy and one to consent. First, ADs' emphasis on precedent autonomy effectively sentences some people who want to live to death. Second, many ADs might not meet the standard criteria for informed refusal of treatment, because they fail on the crucial criterion of sufficient information. Ultimately, it transpires that ADs are typically only appropriate for patients who temporarily lose physical or mental capacity.     

Do Spanish Hospital Professionals Educate Their Patients About Advance Directives?

It is unknown whether hospital-based medical professionals in Spain educate patients about advance directives (ADs). The objective of this research was to determine the frequency of hospital-based physicians’ and nurses’ engagement in AD discussions in the hospital and which patient populations merit such efforts. A short question-and-answer-based survey of physicians and nurses taking care of inpatients was conducted at a university hospital in Madrid, Spain. In total, 283 surveys were collected from medical professionals, of whom 71 per cent were female, with an average age of thirty-four years. Eighty-four per cent had never educated patients about ADs because of lack of perceived responsibility, time, or general knowledge of ADs. Patient populations that warranted AD discussions included those with terminal illnesses (77 per cent), chronic diseases (61 per cent), and elderly patients (43 per cent). Regarding degree of AD understanding in medical professionals: 57 per cent of medical professionals claimed sufficient general knowledge of ADs, 19 per cent understood particulars regarding AD document creation, and 16 per cent were aware of AD regulatory policies. Engagement in AD discussions was considered important by 83 per cent of medical professionals, with 79 per cent interested in participating in such discussions themselves. The majority of hospital physicians and nurses do not educate their patients about ADs, despite acknowledging their importance. Patient populations of highest priority included those with terminal diseases or chronic illness or who are of advanced age.     

ADVANCE DIRECTIVES IN THE NETHERLANDS: AN EMPIRICAL CONTRIBUTION TO THE EXPLORATION OF A CROSS‐CULTURAL PERSPECTIVE ON ADVANCE DIRECTIVES

Research Objective: This study focuses on ADs in the Netherlands and introduces a cross‐cultural perspective by comparing it with other countries. Methods: A questionnaire was sent to a panel comprising 1621 people representative of the Dutch population. The response was 86%. Results: 95% of the respondents didn't have an AD, and 24% of these were not familiar with the idea of drawing up an AD. Most of those familiar with ADs knew about the Advanced Euthanasia Directive (AED, 64%). Both low education and the presence of a religious conviction that plays an important role in one's life increase the chance of not wanting to draw up an AD. Also not having experienced a request for euthanasia from someone else, and the inconceivability of asking for euthanasia yourself, increase the chance of not wanting to draw up an AD. Discussion: This study shows that the subjects of palliative care and end‐of‐life‐decision‐making were very much dominated by the issue of euthanasia in the Netherlands. The AED was the best known AD; and factors that can be linked to euthanasia play an important role in whether or not people choose to draw up an AD. This differentiates the Netherlands from other countries and, when it comes to ADs, the global differences between countries and cultures are still so large that the highest possible goals, at this moment in time, are observing and possibly learning from other cultural settings.     

Las Alpujarras region (South East Spain) HLA genes study: evidence of a probable success of 17th century repopulation from North Spain

Conquest of Granada Muslim Kingdom (1492 AD) finished with Muslim occupation; they were mostly North African Berbers who had reached Iberia by 711 AD. A politics of Iberian Christianization followed after this date: Jewish were expelled in 1492 and Moriscos (Spaniards practicing Muslim religion or speaking Arab) were expelled from all Spanish territory on 1609 AD. Las Alpujarras is a southern Spain mountainous secluded region, which underwent a repopulation from North Spain and a specific Muslim (Moriscos)–Christian war took place according to historical records. Both Las Alpujarras repopulation by northern Iberians and Moriscos expulsion success have been debated and are regarded as non-clarified episodes. In this study, we have addressed the question whether the repopulation succeeded by determining HLA genes of present day Las Alpujarras inhabitants and compared with those of other Mediterranean populations HLA frequencies and genealogies. HLA frequencies show ambiguous results because of extant HLA similar gene frequencies there exist in North Africa and Spain. This is reflected by the finding of North and South western Mediterraneans close relatedness of HLA dendrograms and correspondence analyses. However, the genealogical study of extended HLA haplotypes particularly Alpujarran high frequency of HLA-A29-B44-DRB1*0701-DQA1*02-DQB1*02 (not found in Algerians but frequent in North and Central Spain) and Alpujarran low frequency extended haplotype HLA-A3-B7-DRB1*1501-DQA1*0102-DQB1*0602 (frequent in North Europe) reveals that a significant HLA gene flow from North Spain is observed in present day Alpujarrans: both haplotypes are characteristic of North Spain and North Europe, respectively. This may indicate that enforced Alpujarran repopulation from North Spain may have been a success, which was started by Spanish King Philip II in 1571 AD.     

Antiangiogenic cancer therapy: why do mouse and human patients respond in a different way to the same drug?

The tumor vasculature is an increasingly attractive target for development of anticancer drugs. The fundamental principle for antiangiogenic cancer therapy is based on the inhibitory effect of chemical compounds, proteins or nucleotides on tumor angiogenesis. Indeed, in almost all preclinical tumor models, antiangiogenic monotherapy with different agents shows potent effects on suppression of tumor growth. However, antiangiogenic monotherapy has barely produced any clinical benefits in cancer patients. Although in combination with chemotherapy some antiangiogenic drugs demonstrate survival improvement in patients with certain types of cancers, the overall benefits by addition of antiangiogenic drugs (ADs) to chemotherapy remain modest. The disparity of AD responses between preclinical models and clinical cancer patients has raised important issues, which include: 1) Are current animal tumor models appropriate for assessing the therapeutic efficacy of ADs for clinical development? 2) What are the key differences between mouse tumor models and human cancer patients? 3) Are anti-VEGF drugs off target in cancer patients? 4) What are alternative options for improvement of the clinical benefits of ADs? In this short review, I discuss these critical issues in relation to the clinical practice of ADs.     

Allelic and Genotypic Composition of Ancestral Spanish and Colonial Californian Gene Pools of Avena Barbata: Evolutionary Implications

Spanish explorers and colonists inadvertently started a massive experiment in evolutionary genetics when they accidentally introduced Avena barbata to California from Spain during the seventeenth and eighteenth centuries. Assays of the Spanish and Californian gene pools of this species for 15 loci show that the present day Spanish gene pool, particularly that of Southwestern Spain, is identical or virtually identical to that of California for five loci and closely similar for nine loci. Despite their similar allelic and single-locus genotypic compositions, the present-day Spanish and Californian gene pools are differently structured on a multilocus genetic basis. Evolutionary implications of these results are discussed.     

Constructed identities and Iberia

The category of Iberian identity includes national identities within Spain, Portugal and Latin America. The case of Spain and Spanish national identity has been particularly neglected in academic literature, although this situation has been changing since the mid-1990s, in comparison with analyses of alternative national identities within the Spanish state. This is related the discrediting of Spanish nationalism during the Francoist dictatorship later democratic devolution which encouraged an analogous diversification in the study of national identities within Spain. Since the asymmetric of Spain, Spanish interpretations of nationhood have reflected the premise of the 1978 Constitution that the nation's unity is complemented and strengthened by its national and regional diversity. Variety within broad category of Iberian identities is augmented by the incidence of labour migration into Spain and Portugal and development of popular culture, this case music, in Latin America and specifically Colombia.     

Effect of different diets on the growth and development of Harmonia axyridis (Pallas)

Harmonia axyridis (Pallas) is an important natural enemy of crop pests. Feeding H. axyridis through artificial diets (ADs) is an important means to achieve large-scale production. In this study, the effects of different diets on the growth, development and reproduction of H. axyridis were comprehensively evaluated, and the reasons for the reduced reproductive capacity of H. axyridis fed ADs were preliminarily explored. Artificial diets were prepared using pig liver and pork as the main ingredients. Larval duration, larval survival rate, egg production and other traits were comprehensively evaluated. Harmonia axyridis fed ADs during both the larval and adult periods completed growth and development from larva to adult but had a prolonged development duration (6.13-day extension) and reduced survival rate (15.3% reduction) in the larval stage. In addition, adults could not lay eggs. Next, individuals of H. axyridis were fed Megoura japonica (Matsumura) in the larval stage and an AD, adequate aphids (AA) or an artificial diet plus 5 (AD5), 10 (AD10) or 25 (AD25) aphids in the adult stage. The adults in the AD group produced a small number of eggs (103.3 eggs). When aphids were added to the diet, egg production gradually increased with the number of aphids added. The AD25 group exhibited no significant difference in egg production compared with that in the AA group (983.8 eggs and 1,158.3 eggs, respectively). Anatomical observations of the H. axyridis adults in these five groups revealed that ovary development was slowest in the AD group. In addition, we found that the levels of vitellogenin and juvenile hormone were significantly lower in the AD group than in the AA group. These results provide a foundation for formulating ADs for H. axyridis and improving the large-scale reproduction of this species.     

Disturbance of motivated behavior in rats by epileptic afterdischarges

Nearly all epileptic seizures in patients are characterized by deranged consciousness. We started to study changes in motivated behavior (drinking in thirsty rats) as a possible analogue of compromised consciousness during and after epileptic seizures. Epileptic afterdischarges (ADs) were elicited by stimulation of the dorsal hippocampus and/or thalamus. Rats with implanted electrodes (deprived of water for 24 hours) were trained to lick water from a narrow tube. After pretraining ADs were elicited eight times in each animal and access to water was allowed during different phases of the AD. Stimulation did not affect licking if no AD was induced. If stimulation was successful, licking was stopped in nearly 70 % of stimulations and modified (biting the tube) in 30 %. Hippocampal ADs (characterized by serrated waves in the EEG and by an arrest of behavior with subsequent automatisms) completely blocked licking, signs of recovery appeared during the interval between the AD and recurrent AD and it progressed during recurrent ADs. Thalamic ADs abolished licking in 82% of cases and immediately after ADs normal licking reappeared in 49 % of these observations. Our results suggest that changes in motivated behavior might serve as an analogue of compromised human consciousness.     

Apolipoprotein E region molecular signatures of Alzheimer's disease

Although the APOE region is the strongest genetic risk factor for Alzheimer's diseases (ADs), its pathogenic role remains poorly understood. Elucidating genetic predisposition to ADs, a subset of age‐related diseases characteristic for postreproductive period, is hampered by the undefined role of evolution in establishing molecular mechanisms of such diseases. This uncertainty is inevitable source of natural‐selection–free genetic heterogeneity in predisposition to ADs. We performed first large‐scale analysis of linkage disequilibrium (LD) structures characterized by 30 polymorphisms from five genes in the APOE 19q13.3 region (BCAM, NECTIN2, TOMM40, APOE, and APOC1) in 2,673 AD‐affected and 16,246 unaffected individuals from five cohorts. Consistent with the undefined role of evolution in age‐related diseases, we found that these structures, being highly heterogeneous, are significantly different in subjects with and without ADs. The pattern of the difference represents molecular signature of AD comprised of single nucleotide polymorphisms (SNPs) from all five genes in the APOE region. Significant differences in LD in subjects with and without ADs indicate SNPs from different genes likely involved in AD pathogenesis. Significant and highly heterogeneous molecular signatures of ADs provide unprecedented insight into complex polygenetic predisposition to ADs in the APOE region. These findings are more consistent with a complex haplotype than with a single genetic variant origin of ADs in this region.     

Epidemiological risk factors of Aujeszky’s disease in wild boars (<Emphasis Type="Italic">Sus scrofa</Emphasis>) and domestic pigs in Spain

An Aujeszky’s disease (AD) control and eradication campaign started in Spain in 1995, and as a result, AD virus (ADV) seroprevalences have notably diminished in Spanish domestic pig herds, but eradication has not yet been achieved. Since the presence of ADV in Spanish wild boar populations can impede schemes to eradicate ADV in domestic pig, we conducted analyses of risk factors and investigated associations between the patterns of ADV seroprevalence at the municipal level in the wild boar and the domestic pig, respectively, in south-central Spain. There was a clear influence of individual factors on the risk of wild boar to test positive to ADV. Concerning the domestic pig, higher ADV seroprevalences were observed with increasing numbers of pigs per farm. Indoor pig farms showed higher seroprevalences than open-air farms. Our results show that, at least at the study scale, the level of ADV seroprevalence in domestic pig farms is not influenced by the level of ADV seroprevalence in the coexisting wild boar populations. Also, there was no influence of domestic pigs ADV seroprevalence on the risk of wild boars to test seropositive. Finally, there was no evidence for a statistical association between ADV seroprevalence levels in wild boar and domestic pig at the municipal level in the study region. These findings are of interest for both veterinary and public health authorities. Nevertheless, more effort is needed in order to elucidate the nature of particular ADV outbreaks in domestic pigs in the study region due to possible contacts with wild boars, which will probably require a molecular approach.     

Hippocampal afterdischarges in rats. I. Effects of antiepileptics

Hippocampal afterdischarges (ADs) are considered to be a model of complex partial seizures. To study the pharmacology of these ADs, stimulation electrodes were implanted into the dorsal hippocampus of 33 male Wistar rats. Stimulation (15-s series of monophasic rectangular pulses with a duration of 1 ms and frequency of 8 Hz) was applied four times with interstimulation intervals of 15 min. Drugs (carbamazepine 50 and 100 mg/kg; clonazepam 0.2 and 0.5 mg/kg; ethosuximide 125 and 250 mg/kg; phenobarbital 40 and 80 mg/kg) as well as solvent and isotonic saline were injected intraperitoneally 2 min after the cessation of the first AD. Duration of AD, of the latent period between AD and recurrent AD and duration of recurrent AD and the number of wet dog shakes were measured. ADs were markedly shortened by both doses of clonazepam and phenobarbital and by the higher dose of carbamazepine. The action of ethosuximide was negligible. Wet dog shakes were influenced in the same way as AD duration. Recurrent ADs were more sensitive to antiepileptics than ADs and wet dog shakes.     

Use of macroinvertebrate-based multimetric indices for water quality evaluation in Spanish Mediterranean rivers: an intercalibration approach with the IBMWP index

For the European Parliament and Commission to implement the Water Framework Directive (WFD), the water-quality indices that are currently used in Europe need to be compared and calibrated. This will facilitate the comparative assessment of ecological status throughout the European Union. According to the WFD, biologic indices should respond consistently to human impacts, using multimetric approaches and water-quality classification boundaries adjusted to a common set of normative definitions. The European Commission has started an intercalibration exercise to review biologic indices and harmonize class boundaries. We used data from rivers in Spain to compare the IBMWP (Iberian Biological Monitoring Working Party) index, which is commonly used by water authorities in Spain and by several research centers, with the Intercalibration Common Multimetric Index (ICM-Star), which was used as a standard in the intercalibration exercise. We also used data from Spanish rivers to compare the multimetric indices ICM-7 (based on quantitative data) and ICM-9 (based on qualitative data) with the IBMWP. ICM-7 and ICM-9 were proposed by the Mediterranean Geographical Intercalibration Group (Med-GIG). Additionally, we evaluated two new multimetric indices, developed specifically for macroinvertebrate communities inhabiting Mediterranean river systems. One of these is based on quantitative data (ICM-10), while the other is based on qualitative data (ICM-11a). The results show that the IBMWP index responds well to the stressor gradient present in our data, and correlates well with ICM-Star. Moreover, the IBMWP quality class boundaries were consistent with the intercalibration requirements of the WFD. However, multimetric indices showed a more linear relation with the stressor gradient in our data, and less variation in reference values. In addition, they may provide more statistical power for detecting potential environmental impacts. Multimetric indices produced similar results for quantitative and qualitative data. Thus, ICM-10 (also named IMMi-T) and ICM-11a (also named IMMi-L) indices could be used to meet European Commission requirements for assessing the water quality in Spanish Mediterranean rivers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Handling editor: Joel Trexler     

The impact of different types of assistive devices on gait measures and safety in Huntington's disease

Background

Gait and balance impairments lead to frequent falls and injuries in individuals with Huntington''s disease (HD). Assistive devices (ADs) such as canes and walkers are often prescribed to prevent falls, but their efficacy is unknown. We systematically examined the effects of different types of ADs on quantitative gait measures during walking in a straight path and around obstacles.

Methods

Spatial and temporal gait parameters were measured in 21 subjects with HD as they walked across a GAITRite walkway under 7 conditions (i.e., using no AD and 6 commonly prescribed ADs: a cane, a weighted cane, a standard walker, and a 2, 3 or 4 wheeled walker). Subjects also were timed and observed for number of stumbles and falls while walking around two obstacles in a figure-of-eight pattern.

Results

Gait measure variability (i.e., coefficient of variation), an indicator of fall risk, was consistently better when using the 4WW compared to other ADs. Subjects also walked the fastest and had the fewest number of stumbles and falls when using the 4WW in the figure-of-eight course. Subjects walked significantly slower using ADs compared to no AD both across the GAITRite and in the figure-of-eight. Measures reflecting gait stability and safety improved with the 4WW but were made worse by some other ADs.     

Antidepressants and breast and ovarian cancer risk: a review of the literature and researchers' financial associations with industry

Background

Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results [1]–[6]. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions [7].

Methods and Findings

We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (through November 2010). A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers'' financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03–1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher''s Exact test P = 0.0012).

Conclusions

Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the informed consent process.     

Induction of c-fos mRNA Expression by Afterdischarge in the Hippocampus of Naive and Kindled Rats

Periodic induction of focal electrical seizure [afterdischarge (AD)] is an absolute prerequisite for the development of kindling, an animal model of complex partial epilepsy. Once established, it is a permanent condition. The mechanism(s) that translate ADs, which last tens of seconds, into life-long alterations in the CNS is unclear. Cellular immediate-early genes have been implicated in the conversion of short-term stimuli to long-term alterations in cellular phenotypes by regulating target gene expression. We have investigated the contribution of one such early gene, c-fos, to this process. The relationship between ADs and expression of c-fos gene in the rat hippocampus, a key structure in kindling development, was studied by analysis of mRNA levels. The low constitutive expression of c-fos mRNA in the hippocampus was not altered by kindling. There was an "all-or-none" relationship between induction of c-fos and the duration of AD. The threshold for induction was approximately 30 s of AD. Above-threshold ADs induced c-fos in both naive and kindled animals to the same extent and with identical temporal profiles. Although the expression of c-fos is unchanged with kindling, c-fos may nonetheless contribute to many long-term changes of kindling, both adaptive and epileptogenic.     

Presencia y representación de las personas mayores en la publicidad televisiva: el caso español

Introduction

The demographic shift towards aging population generates a series of socioeconomic and cultural changes that are beginning to transform the role and public image of older people. The elderly have become one of the market segments with a greater future. This fact has attracted little scientific interest in the field of advertising communication and for this reason there is little research that is actually looking into this Spain. This research examines the use that is made of the image of the elderly in the television advertising in Spain, looking at the differences between the advertisement dedicated to the targeting people over 65, and those that are not directed at the elderly, but use older people in their content as actors or main characters in the advertisement.

Material and methods

A content analysis study was conducted on a sample of 2,065 spots obtained from prime time slots (from 20:30 to 22:30 p.m.) from the five major Spanish television channels (TVE 1, La 2, Tele 5, Antena 3 and Cuatro). Two independent judges coded all the advertisements. The reliability coefficient between judges was 0.91.

Results and conclusions

In general, older people, particularly women, are not very often shown in Spanish advertising. Their presence is much stronger and visible in campaigns which aim their communication strategy at different age groups. In those cases, advertising presents the elderly with a stereotyped, self-interested and traditional image.     

Large extracellular space leads to neuronal susceptibility to ischemic injury in a Na<Superscript>+</Superscript>/<Emphasis Type="Bold">K</Emphasis><Superscript>+</Superscript> pumps–dependent manner

The extent of anoxic depolarization (AD), the initial electrophysiological event during ischemia, determines the degree of brain region–specific neuronal damage. Neurons in higher brain regions exhibiting nonreversible, strong AD are more susceptible to ischemic injury as compared to cells in lower brain regions that exhibit reversible, weak AD. While the contrasting ADs in different brain regions in response to oxygen–glucose deprivation (OGD) is well established, the mechanism leading to such differences is not clear. Here we use computational modeling to elucidate the mechanism behind the brain region–specific recovery from AD. Our extended Hodgkin–Huxley (HH) framework consisting of neural spiking dynamics, processes of ion accumulation, and ion homeostatic mechanisms unveils that glial–vascular K⁺ clearance and Na⁺/K⁺–exchange pumps are key to the cell’s recovery from AD. Our phase space analysis reveals that the large extracellular space in the upper brain regions leads to impaired Na⁺/K⁺–exchange pumps so that they function at lower than normal capacity and are unable to bring the cell out of AD after oxygen and glucose is restored.