Package inserts for prescribed medicines: what minimum information do patients need?

The information a patient needs about a prescribed medicine can be determined by considering what responsibilities he can assume in relation to taking medicine. When the medicine has been dispensed the patient needs to know how to take the drug; how to store the drug; how it is expected to help; and how to recognise problems and what to do about them. A guide was designed to specify what information is required to meet these needs. Using this guide, a set of minimum information on tetracycline was prepared that aimed at being brief, specific, and readable. The best format for the information remains to be determined. Since leaflets produced by professional organisations are generally unsuitable for these purposes, information sets should be put together by small independent groups consisting of clinical pharmacologists, clinicians, pharmacists, and consumers. Each country should produce its own sets, adapting model sets to the circumstances of local practice.     

Birds and prehistoric agriculture: The New Mexican pueblos

Analysis of faunal remains from prehistoric southwestern pueblo sites reveals certain commonly occurring species of mammals and birds, the latter including ducks and geese, hawks and eagles, American Kestrel, Mourning Dove, owls, Horned Lark, Common Raven, and jays. This phenomenon is examined with the analysis of bird bones from four New Mexican pueblos located in north-central and west-central New Mexico. Recovered faunal remains date to specific periods between A.D. 1250 and the present. Over 70 species of birds represent various ecological situations; many of these species presently do not occur near the pueblos and a few occur only in the extreme southeastern portion of the state. Marsh and riparian areas along the river systems and richer grasslands on the floodplains would account for most of these species occurring near the sites prehistorically. However, rather than attribute unusual species to climatic change, trade, or long-distance hunting expeditions by the Indians, an alternative explanation is offered which attributes high species diversity to areas of human disturbance. Disturbed areas such as agricultural fields can increase species diversity in an area and aid in the range extension of many animals. The primary factor in this situation, besides the crops themselves, is believed to be insects, which attract other animals, particularly birds and their predators. In addition, field irrigation systems act to extend riparian growth from the river across the floodplain, creating habitats for these animals. Finally, certain groups of birds and mammals have developed a natural attraction to human settlements and agricultural areas and these include species whose remains commonly occur in prehistoric pueblo sites. The avifauna from these sites also reveals information on the prehistoric use of birds as inferred from bone modification, cut marks, burials, and articulated wings.     

Activin signalling and pre-eclampsia: From genetic risk to pre-symptomatic biomarker

Pre-eclampsia is a multi-system condition in pregnancy that is characterised by the onset of hypertension and proteinuria in women after the 20th week and it remains a leading cause of maternal and fetal mortality. Despite this the causative molecular basis of pre-eclampsia remains poorly understood. As a result, an intensive research effort has focused on understanding the molecular mechanisms involved in pre-eclampsia and using this information to identify new pre-symptomatic bio-markers of the condition. Activin A and its receptor, ACVR2A, have been extensively studied in this regard.Activin A is a member of the transforming growth factor (TGF)-β superfamily that has a wide range of biological functions depending on the cellular context. Recent work has shown that polymorphisms in ACVR2A may be a genetic risk factor for pre-eclampsia. Furthermore, both placenta and serum levels of Activin A are significantly increased in pre-eclampsia suggesting that Activin A may be a possible biomarker for the condition. Here we review the latest advances in this field and link these with new molecular data that suggest that the oxidative stress and pro-inflammatory cytokine production seen in pre-eclampsia may result in increased placental Activin A secretion in an attempt to maintain placental function.     

The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis?

There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for this “HDL hypothesis”. In vitro studies suggest that HDL has a wide range of anti-atherogenic properties but validation of these functions in humans is absent to date. A significant number of animal studies and clinical trials support an atheroprotective role for HDL; however, most of these findings were obtained in the context of marked changes in other plasma lipids. Finally, genetic studies in humans have not provided convincing evidence that HDL genes modulate cardiovascular risk. Thus, despite a wealth of information on this intriguing lipoprotein, future research remains essential to prove the HDL hypothesis correct.     

Age estimation from stages of epiphyseal union in the presacral vertebrae

The presacral vertebrae have various secondary centers of ossification, whose timing of fusion can be used for age estimation of human skeletal remains up to the middle to the latter third decade. However, detailed information about the age at which these secondary centers of ossification fuse has been lacking. In this study, the timing of epiphyseal union in presacral vertebrae was studied in a sample of modern Portuguese skeletons (57 females and 47 males) between the ages of 9 and 30, taken from the Lisbon documented skeletal collection. A detailed photographic record of these epiphyses and the age ranges for the different stages of epiphyseal union are provided. Partial union of epiphyses was observed from 11 to 27 years of age. In general, centers of ossification begin to fuse first in the cervical and lumbar vertebrae, followed by centers of ossification in the thoracic region. The first center of ossification to complete fusion is usually that of the mammillary process in lumbar vertebrae. This is usually followed by that of the transverse process, spinous transverse process, and annular ring, regardless of vertebra type. There were no statistically significant sex differences in timing of fusion, but there was a trend toward early maturation in females for some vertebra or epiphyses. Bilateral epiphyses did not show statistically significant differences in timing of fusion. This study offers information on timing of fusion of diverse epiphyseal locations useful for age estimation of complete or fragmented human skeletal remains. Am J Phys Anthropol, 2011. © 2010 Wiley‐Liss, Inc.     

HORSETAILS AND SEED FERNS FROM THE MIDDLE TRIASSIC (ANISIAN) LOCALITY KÜHWIESENKOPF (MONTE PRÀ DELLA VACCA), DOLOMITES, NORTHERN ITALY

Abstract:  Well-preserved floras from the Alpine Early–Middle Triassic are rare, and thus our understanding of the vegetation in this area during this period of time continues to be incomplete. As a result, every new find represents a significant piece of information that deserves thoughtful consideration. Anisian (Middle Triassic) sphenophytes and pteridosperms have recently been recovered from the Kühwiesenkopf locality (Monte Prà della Vacca) in northern Italy. The sphenophytes are represented by stem fragments, strobili and isolated sporangiophore heads of Equisetites , as well as by a few specimens of Neocalamites sp. and Echinostachys sp. The pteridosperms include abundant remains of the peltasperm foliage type Scytophyllum bergeri . A second Scytophyllum species in this flora, S. apoldense , is regarded as conspecific with S. bergeri based on epidermal anatomy; the two morphotypes are interpreted as sun and shade leaves of a single biological species. The seed-bearing disc Peltaspermum bornemannii sp. nov. probably represents the female reproductive structure of S. bergeri . Additional pteridosperm remains include foliage assignable to Sagenopteris sp. and Ptilozamites sp., in both cases perhaps the earliest records of these genera.     

Analysis of changes in the beat-to-beat P-wave morphology using clustering techniques

Several pathologies related to the atrial electrical activity can be detected in the electrocardiogram P-wave. A protocol for analyzing P-wave morphology changes has been developed in this article. By using this protocol a study on the beat-to-beat P-wave morphology changes of 89 ECG signals is performed. An algorithm based on the embedding space techniques has been used to extract the P-wave information of the ECG. The P-waves obtained in several of these ECGs exhibit significant alternate morphology changes. The morphologies have been classified by using the K-means clustering algorithm. The mechanism behind the P-wave morphology change process and its possible pathophysiological importance remains to be clarified.     

First archaeozoological identification of Atlantic sturgeon (Acipenser oxyrinchus Mitchill 1815) in France

To this day, the only sturgeon to be listed on the French vertebrate inventory is the European sturgeon (Acipenser sturio Linnaeus, 1758). The recent study of sturgeon remains on various French archaeological sites shows the presence of another species: the Atlantic sturgeon (A. oxyrinchus Mitchill 1815). This species already existed in the French Atlantic region at the end of the Neolithic Age 5000 years ago and was still to be found 3000 years later. Thus the A. oxyrinchus determined in several Baltic medieval sites are neither the only nor the first sturgeons to have inhabited European waters. Sturgeon restoration projects in European rivers necessitate a precise determination of the native species. In the case of relict or extinct species, the bone remains found on archaeological sites represent the most reliable source of information. This discovery will also be the starting point of palaeogenetical research (mitochondrial and cellular aDNA) and will give information about the genetic diversity of these threatened or recently extinct populations.     

THE AUDITORY REGION OF EARLY PALEOCENE PUCADELPHYDAE (MAMMALIA, METATHERIA) FROM TIUPAMPA, BOLIVIA, WITH PHYLOGENETIC IMPLICATIONS

Abstract:  New petrosal bones, assigned to Pucadelphys and Andinodelphys , from the Lower Paleocene of Tiupampa, Bolivia, are described. These remains provide new information on the anatomy of the ear region of these taxa. The re-examination of characters from the petrosal and basicranium shed light on the phylogenetic relationships of the three Tiupampan genera known from complete cranial remains (i.e. Mayulestes , Pucadelphys and Andinodelphys ). The combination of dental, general cranial and basicranial characters led to two alternative hypotheses. The first is that borhyaenoids (including Mayulestes ) are nested within Notometatheria. Pucadelphyds (i.e. Pucadelphys and Andinodelphys ) are the sister group of a clade comprising MHNC 8369 (one isolated petrosal from Tiupampa) and Marsupialia. The second favours the paraphyly of 'borhyaenoids' (i.e. the exclusion of Mayulestes from borhyaenoids) and the polyphyly of 'Notometatheria'. In this case, Mayulestes and borhyaenids represent the stem group of a clade including Asiatic, American and Australian metatherians. This analysis of combined datasets (dental, general cranial and basicranial) highlighted contradictory information in the dental and cranial characters, serving to emphasize that in a large anatomical complex like an entire skull mosaic evolution of the characters is likely.     

Positional information in neural map development: lessons from the olfactory system

Positional information is fundamental in development. Although molecular gradients are thought to represent positional information in various systems, the molecular logic used to interpret these gradients remains controversial. In the nervous system, sensory maps are formed in the brain based on gradients of axon guidance molecules. However, it remains unclear how axons find their targets based on relative, not absolute, expression levels of axon guidance receptors. No model solely based on axon-target interactions explains this point. Recent studies in the olfactory system suggested that the neural map formation requires axon-axon interactions, which is known as axon sorting. This review discusses how axon-axon and axon-target interactions interpret molecular gradients and determine the axonal projection sites in neural map formation.     

Deciphering archaeological palimpsests with bone micro-fragments from the Lower Magdalenian of El Mirón cave (Cantabria,Spain)

Abstract

Modern excavation techniques aim accurately to recover extant archaeological data. Usually bone micro-fragments are gathered as a result, however, during archaeological analysis these remains are often set apart as indeterminate bones and generally do not contribute to the interpretation of the deposits. How to decipher archaeological palimpsests using these small bone fragments is the aim of this paper. El Mirón Cave, located in northern Iberia, contains a very rich Cantabrian Lower Magdalenian deposit (17–15 uncal ka BP) with high densities of faunal remains and artefacts. Here, we present zooarchaeological, taphonomic and spatial distribution analyses of macromammal finds, including those small bone fragments, accumulated during a series of intensive and repeated human occupations found in the outer vestibule excavation area. Our results show that a broad spectrum of activities was performed there, including meat, marrow and grease processing and waste abandonment. We propose that bone micro-fragments must be considered when addressing human subsistence reconstructions from animal remains, as they represent the leftovers of the chaîne opératoire of animal carcass exploitation. The archaeological implications of their inclusion are extremely valuable, especially when deciphering palimpsests. A multidisciplinary approach to study these small animal remains provides information that otherwise would be missed.     

Almost 20 years of Neanderthal palaeogenetics: adaptation,admixture, diversity,demography and extinction

Nearly two decades since the first retrieval of Neanderthal DNA, recent advances in next-generation sequencing technologies have allowed the generation of high-coverage genomes from two archaic hominins, a Neanderthal and a Denisovan, as well as a complete mitochondrial genome from remains which probably represent early members of the Neanderthal lineage. This genomic information, coupled with diversity exome data from several Neanderthal specimens is shedding new light on evolutionary processes such as the genetic basis of Neanderthal and modern human-specific adaptations—including morphological and behavioural traits—as well as the extent and nature of the admixture events between them. An emerging picture is that Neanderthals had a long-term small population size, lived in small and isolated groups and probably practised inbreeding at times. Deleterious genetic effects associated with these demographic factors could have played a role in their extinction. The analysis of DNA from further remains making use of new large-scale hybridization-capture-based methods as well as of new approaches to discriminate contaminant DNA sequences will provide genetic information in spatial and temporal scales that could help clarify the Neanderthal''s—and our very own—evolutionary history.     

Human tooth wear, tooth function and cultural variability

Among primitive peoples dental attrition appears to be a natural phenomenon. Often the degrees and kinds of tooth wear vary from population to population. This variability is possibly related to certain material aspects of culture such as diet, food preparation techniques and tool usage. In order to learn more about these relationships, extensive cross cultural comparisons must be made. This paper reports on a study of dental attrition among skeletal remains of North American Indians from three areas: California, the Southwest and the Valley of Mexico. A method of comparing worn teeth of these populations was devised so several characteristics of the teeth and supporting bone could be examined by population. This study showed significant differences in type and degree of wear among the three groups as well as differences between sexes within each population. A positive correlation between tooth wear and cultural factors was found. Dietary specialization and division of labor appear to be responsible for the degree and type of wear found in this sample. Further studies of this type are planned to expand the sample size and, if the new data support these correlations, valuable information about human–environmental relationships can be gained.     

Finding the evidence for protein-protein interactions from PubMed abstracts

MOTIVATION: Protein-protein interactions play critical roles in biological processes, and many biologists try to find or to predict crucial information concerning these interactions. Before verifying interactions in biological laboratory work, validating them from previous research is necessary. Although many efforts have been made to create databases that store verified information in a structured form, much interaction information still remains as unstructured text. As the amount of new publications has increased rapidly, a large amount of research has sought to extract interactions from the text automatically. However, there remain various difficulties associated with the process of applying automatically generated results into manually annotated databases. For interactions that are not found in manually stored databases, researchers attempt to search for abstracts or full papers. RESULTS: As a result of a search for two proteins, PubMed frequently returns hundreds of abstracts. In this paper, a method is introduced that validates protein-protein interactions from PubMed abstracts. A query is generated from two given proteins automatically and abstracts are then collected from PubMed. Following this, target proteins and their synonyms are recognized and their interaction information is extracted from the collection. It was found that 67.37% of the interactions from DIP-PPI corpus were found from the PubMed abstracts and 87.37% of interactions were found from the given full texts. AVAILABILITY: Contact authors.     

Integrated information increases with fitness in the evolution of animats

One of the hallmarks of biological organisms is their ability to integrate disparate information sources to optimize their behavior in complex environments. How this capability can be quantified and related to the functional complexity of an organism remains a challenging problem, in particular since organismal functional complexity is not well-defined. We present here several candidate measures that quantify information and integration, and study their dependence on fitness as an artificial agent ("animat") evolves over thousands of generations to solve a navigation task in a simple, simulated environment. We compare the ability of these measures to predict high fitness with more conventional information-theoretic processing measures. As the animat adapts by increasing its "fit" to the world, information integration and processing increase commensurately along the evolutionary line of descent. We suggest that the correlation of fitness with information integration and with processing measures implies that high fitness requires both information processing as well as integration, but that information integration may be a better measure when the task requires memory. A correlation of measures of information integration (but also information processing) and fitness strongly suggests that these measures reflect the functional complexity of the animat, and that such measures can be used to quantify functional complexity even in the absence of fitness data.     

Use of complement inhibitors in tissue injury

A great deal of information has accumulated implicating the complement system in several human disease processes. Although some of this information is circumstantial, protein inhibitors of the complement system have been developed and applied successfully to experimental disease models in animals. Two inhibitors, soluble complement receptor 1 (sCR1) and anti-C5 monoclonal antibody, are now being investigated in a variety of clinical conditions such as systemic lupus erythematosus and rheumatoid arthritis (RA), diseases for which current therapy has changed little and remains unsatisfactory. Preliminary successes in Phase II clinical trials of RA have provided optimism that complement inhibition might prove useful in these diseases and become part of standard medical therapy.     

Age and sex bias in the reconstruction of past population structures

Palaeodemographical studies are founded on the assumption that the sex and age distribution of the skeletal sample reflects the constitution of the original population. It is becoming increasingly clear, however, that the type and amount of information that may be derived from osteoarchaeological collections are related to the state of preservation of remains. This work proposes a new method to evaluate bone preservation, to identify age and sex biases in the preservation of human skeletal remains, and to assess whether differences in preservation patterns are more dependent on factors intrinsic or extrinsic to anatomical features of human bones. Three osteological collections and over 600 skeletons were observed. The state of preservation of human bones was assessed using three preservation indexes: the anatomical preservation index (API), the bone representation index (BRI), and the qualitative bone index (QBI). The results suggest that subadult skeletons are generally more poorly preserved and with bones less well-represented than adult skeletons. Among subadults, female and male skeletons have different patterns of preservation according to their age. This pattern of preservation depends on intrinsic anatomical properties of bones themselves, while external factors can only increase these differences in the state of preservation and representation of osseous remains. It is concluded from this that failure to recognize these differences may lead to misleading interpretations of paleodemography of past human populations.     

Life expectancy of the 20th century Venda: A compilation of skeletal and cemetery data

Little information is available on the 20th century mortality rates of rural black South African groups, such as the Venda. The purpose of this study was to apply abridged life tables in order to estimate life expectancy from both skeletal remains and death registry information of modern South African communities. Comparisons were also made with prehistoric and contemporary groups as a means to better evaluate life expectancy for this time period. The sample consisted of 160 skeletons of known Venda origin and burial registry information for 1364 black South Africans from the Rebecca Street and Mamelodi Cemeteries in Pretoria, South Africa. Standard anthropological techniques were applied to determine sex and estimate age from the skeletal remains. The stationary and non-stationary life table models were used to analyse the data. A high rate of child mortality, low juvenile and adult mortality with a steady increase in mortality after the age of 30 years was observed for both the Venda and the cemetery samples. Throughout the 20th century, life expectancy was shown to increase for black South Africans. However, due to the widespread HIV infection/AIDS of the 21st century, infant and young adult mortality rates continue to rise at such a speed that the decline in mortality seen for South Africans in the last 50 years will most likely to be lost in the next decade due to this disease.     

Contrôle neurologique de l’éjaculation

The brain control of the genital tract and sexual behaviour remains poorly understood. Clinical results and basic research indicate that the neural control of ejaculation depends on three levels of organization. The first level consists of peripheral autonomic and somatic nerves. Leaving the spinal cord, these nerves control the motility, secretions and blood supply of the genital tract, and contractions of perineal striated muscles. Their path in the abdominal cavity and the effects of their neuro-transmitters on peripheral tissues have been established. These nerves also convey sensory information from the genital tract to the spinal cord. The second level is represented by the spinal cord. The thoracolumbar (sympathetic), and sacral (parasympathetic and pudendal) segments of the cord contain the somata of autonomic and somatic motoneurons, whose axons run in the above nerves. These motoneurons are part of a spinal network that likely organizes the activity of the whole genital tract in a given context such as copulation. The role of the different spinal cord segments in the control of ejaculation is mainly inferred from observations of the deleterious effects of spinal cord injury in human patients. A small population of galaninergic positive neurons has recently been identified in the lumbar segments of the rat spinal cord that plays a major role in ejaculation (Truitt and Coolen, 2003). Selective lesion of this population abolishes in copula ejaculations, but spares erection. Finally, the third level of organization is represented by supraspinal nervous structures. The spinal cord receives direct excitatory and inhibitory information from the brainstem, pons and hypothalamus. In turn, these structures receive sensory information from the genital tract. However, their role in the control of ejaculation remains poorly investigated. Again, it is mainly inferred from the observation of the deleterious effects of pharmacological treatments on brain neurotransmission. Positron emission tomography has recently been used to observe brain areas whose activity is enhanced during ejaculation in humans (Holstege et al., 2003). In this study, several areas of the right side of the cortex and the cerebellum were activated. The targets of future clinical and basic research include: the neural basis of the required coordination between spinal autonomic and somatic nuclei that innervate the genital tract, the role of sensory information from the genital tract in the recruitment and coordination of spinal and supraspinal nuclei, and finally the integration of descending excitatory and inhibitory influences onto the spinal cord. Both the organization during development and the activation at puberty of the spinal neural network that controls the genital tract are dependent on androgens. Future research should identify the regulatory factors that, in response to the action of androgens, provide neurons with the possibility of building their connexions and selecting their neurotransmitters and receptors.     

Rab and ARF GTPase regulation of exocytosis

Our understanding of the mechanisms governing of Rab and Arf protein function has exploded in recent years with a convergence of information from model genetic organisms, biochemical studies, cell biological observations and protein structural information. However, the list of known Rab and Arf interacting factors still remains small relative to the number of these small GTPases that have been identified through complete genomic sequencing. It can be anticipated that the factors listed and discussed in this review probably represent a small fraction of the Rab and Arf accessory molecules that remain to be discovered. The identification of regulators and accessory molecules for the Rab and Arf families has allowed investigators to elaborate themes and develop a framework for a mechanistic understanding of these proteins. The themes are highlighted in this review, which aims to concentrate on Rab and Arf function in exocytosis.