32 resultados para Post-registration changes to medicines
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Fish populations are increasingly being subjected to anthropogenic changes to their sensory environments. The impact of these changes on inter- and intra-specific communication, and its evolutionary consequences, has only recently started to receive research attention. A disruption of the sensory environment is likely to impact communication, especially with respect to reproductive interactions that help to maintain species boundaries. Aquatic ecosystems around the world are being threatened by a variety of environmental stressors, causing dramatic losses of biodiversity and bringing urgency to the need to understand how fish respond to rapid environmental changes. Here, we discuss current research on different communication systems (visual, chemical, acoustic, electric) and explore the state of our knowledge of how complex systems respond to environmental stressors using fish as a model. By far the bulk of our understanding comes from research on visual communication in the context of mate selection and competition for mates, while work on other communication systems is accumulating. In particular, it is increasingly acknowledged that environmental effects on one mode of communication may trigger compensation through other modalities. The strength and direction of selection on communication traits may vary if such compensation occurs. However, we find a dearth of studies that have taken a multimodal approach to investigating the evolutionary impact of environmental change on communication in fish. Future research should focus on the interaction between different modes of communication, especially under changing environmental conditions. Further, we see an urgent need for a better understanding of the evolutionary consequences of changes in communication systems on fish diversity.
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2D-3D registration of pre-operative 3D volumetric data with a series of calibrated and undistorted intra-operative 2D projection images has shown great potential in CT-based surgical navigation because it obviates the invasive procedure of the conventional registration methods. In this study, a recently introduced spline-based multi-resolution 2D-3D image registration algorithm has been adapted together with a novel least-squares normalized pattern intensity (LSNPI) similarity measure for image guided minimally invasive spine surgery. A phantom and a cadaver together with their respective ground truths were specially designed to experimentally assess possible factors that may affect the robustness, accuracy, or efficiency of the registration. Our experiments have shown that it is feasible for the assessed 2D-3D registration algorithm to achieve sub-millimeter accuracy in a realistic setup in less than one minute.
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AIM: To evaluate periodontal changes following apical surgery, and to relate changes to the type of incision and to the type of restoration present at the gingival margin (GM). METHODOLOGY: Periodontal parameters [probing depth (PD), level of GM and clinical attachment, plaque and bleeding indices] were recorded at baseline and 1 year following apical surgery. The periodontal changes were calculated and assessed with respect to the incision technique (intrasulcular incision, papilla base incision and submarginal incision), as well as to the presence and type of a restoration margin in contact with the gingiva. RESULTS: One hundred and eighty-four teeth could be evaluated. No significant differences between the three incision techniques were found regarding changes in PDs and plaque index over time. However, significant differences between the intrasulcular and submarginal incisions were found for changes in levels of GM and clinical attachment. For example, with the intrasulcular incision, there was a mean recession of 0.42 mm at buccal sites, whereas using the submarginal incision there was a gain of 0.05 mm. No statistically significant influence could be demonstrated for the presence and type of restoration margins, or the smoking habit of the patient. CONCLUSION: The type of incision was found to affect changes significantly in periodontal parameters within an observation period of 1 year following apical surgery, whereas the restoration margin and smoking habit did not prove to have any significant effect.
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INTRODUCTION: Recent advances in medical imaging have brought post-mortem minimally invasive computed tomography (CT) guided percutaneous biopsy to public attention. AIMS: The goal of the following study was to facilitate and automate post-mortem biopsy, to suppress radiation exposure to the investigator, as may occur when tissue sampling under computer tomographic guidance, and to minimize the number of needle insertion attempts for each target for a single puncture. METHODS AND MATERIALS: Clinically approved and post-mortem tested ACN-III biopsy core needles (14 gauge x 160 mm) with an automatic pistol device (Bard Magnum, Medical Device Technologies, Denmark) were used for probe sampling. The needles were navigated in gelatine/peas phantom, ex vivo porcine model and subsequently in two human bodies using a navigation system (MEM centre/ISTB Medical Application Framework, Marvin, Bern, Switzerland) with guidance frame and a CT (Emotion 6, Siemens, Germany). RESULTS: Biopsy of all peas could be performed within a single attempt. The average distance between the inserted needle tip and the pea centre was 1.4mm (n=10; SD 0.065 mm; range 0-2.3 mm). The targets in the porcine liver were also accurately punctured. The average of the distance between the needle tip and the target was 0.5 mm (range 0-1 mm). Biopsies of brain, heart, lung, liver, pancreas, spleen, and kidney were performed on human corpses. For each target the biopsy needle was only inserted once. The examination of one body with sampling of tissue probes at the above-mentioned locations took approximately 45 min. CONCLUSIONS: Post-mortem navigated biopsy can reliably provide tissue samples from different body locations. Since the continuous update of positional data of the body and the biopsy needle is performed using optical tracking, no control CT images verifying the positional data are necessary and no radiation exposure to the investigator need be taken into account. Furthermore, the number of needle insertions for each target can be minimized to a single one with the ex vivo proven adequate accuracy and, in contrast to conventional CT guided biopsy, the insertion angle may be oblique. Navigation for minimally invasive tissue sampling is a useful addition to post-mortem CT guided biopsy.
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AIM: This study was conducted to delineate partnership-relation functioning over time and specifically matched to various organs such as heart, liver, and kidney. METHOD: Prospective, paralleled case-control-study including patients and their respective partners before and one year after organ transplantation in 23 heart-transplant recipients, 19 liver-transplant patients, and 16 kidney-transplant recipients. To assess partnership functioning, the FB-Z (family assessment measure) of Cierpka and Frevert was used. Statistics included descriptive methods, correlations, and analysis of variance including the items "organ" and "time". RESULTS: Heart-transplant recipients and their partners show significant better overall measures in their partnership ratings (sum-value) in comparison to liver or kidney patients and their partners. In all patient and partner groups, except in kidney-transplant recipients a significant deterioration over time is discernible in the subscales role performance and emotionality. In respect to the item "organ" significant differences were found in overall functioning and the subscale communication where heart-transplant recipients and their partners have significant better functioning compared to kidney or liver transplant patients. In kidney patients and their partners only communication changes to the better in the time course. CONCLUSION: In any organ transplantation the two sides of the coin are important to bear in mind, the one is the live-saving act of transplantation as such, the other is the important distress in the phase before but equally after the operation, mainly in the first year where patients and their respective partners have to be followed and treated even in respect to psychosocial and marital functioning.
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Post-natal exposure to air pollution is associated with diminished lung growth during school age. The current authors aimed to determine whether pre-natal exposure to air pollution is associated with lung function changes in the newborn. In a prospective birth cohort of 241 healthy term-born neonates, tidal breathing, lung volume, ventilation inhomogeneity and exhaled nitric oxide (eNO) were measured during unsedated sleep at age 5 weeks. Maternal exposure to particles with a 50% cut-off aerodynamic diameter of 10 microm (PM(10)), nitrogen dioxide (NO(2)) and ozone (O(3)), and distance to major roads were estimated during pregnancy. The association between these exposures and lung function was assessed using linear regression. Minute ventilation was higher in infants with higher pre-natal PM(10) exposure (24.9 mL x min(-1) per microg x m(-3) PM(10)). The eNO was increased in infants with higher pre-natal NO(2) exposure (0.98 ppb per microg x m(-3) NO(2)). Post-natal exposure to air pollution did not modify these findings. No association was found for pre-natal exposure to O(3) and lung function parameters. The present results suggest that pre-natal exposure to air pollution might be associated with higher respiratory need and airway inflammation in newborns. Such alterations during early lung development may be important regarding long-term respiratory morbidity.
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BACKGROUND: The provision of highly active antiretroviral therapy (HAART) in resource-limited settings follows a public health approach, which is characterised by a limited number of regimens and the standardisation of clinical and laboratory monitoring. In industrialized countries doctors prescribe from the full range of available antiretroviral drugs, supported by resistance testing and frequent laboratory monitoring. We compared virologic response, changes to first-line regimens, and mortality in HIV-infected patients starting HAART in South Africa and Switzerland. METHODS AND FINDINGS: We analysed data from the Swiss HIV Cohort Study and two HAART programmes in townships of Cape Town, South Africa. We included treatment-naïve patients aged 16 y or older who had started treatment with at least three drugs since 2001, and excluded intravenous drug users. Data from a total of 2,348 patients from South Africa and 1,016 patients from the Swiss HIV Cohort Study were analysed. Median baseline CD4+ T cell counts were 80 cells/mul in South Africa and 204 cells/mul in Switzerland. In South Africa, patients started with one of four first-line regimens, which was subsequently changed in 514 patients (22%). In Switzerland, 36 first-line regimens were used initially, and these were changed in 539 patients (53%). In most patients HIV-1 RNA was suppressed to 500 copies/ml or less within one year: 96% (95% confidence interval [CI] 95%-97%) in South Africa and 96% (94%-97%) in Switzerland, and 26% (22%-29%) and 27% (24%-31%), respectively, developed viral rebound within two years. Mortality was higher in South Africa than in Switzerland during the first months of HAART: adjusted hazard ratios were 5.90 (95% CI 1.81-19.2) during months 1-3 and 1.77 (0.90-3.50) during months 4-24. CONCLUSIONS: Compared to the highly individualised approach in Switzerland, programmatic HAART in South Africa resulted in similar virologic outcomes, with relatively few changes to initial regimens. Further innovation and resources are required in South Africa to both achieve more timely access to HAART and improve the prognosis of patients who start HAART with advanced disease.
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The S218L CACNA1A mutation has been previously described in two families with familial hemiplegic migraine. We present three siblings with the mutation with the novel association of childhood seizures, and highlight the dynamic changes seen on electroencephalography during hemiplegic migraine attacks. Depressed activity contralateral to the hemiparesis was seen on electroencephalography during acute hemiplegic migraine attacks, which may be due to changes to calcium channels caused by the S218L mutation. Both parents were asymptomatic and did not carry the S218L mutation in their blood. This suggests the presence of mosaicism in the transmitting parent.
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As domain-specific modeling begins to attract widespread acceptance, pressure is increasing for the development of new domain-specific languages. Unfortunately these DSLs typically conflict with the grammar of the host language, making it difficult to compose hybrid code except at the level of strings; few mechanisms (if any) exist to control the scope of usage of multiple DSLs; and, most seriously, existing host language tools are typically unaware of the DSL extensions, thus hampering the development process. Language boxes address these issues by offering a simple, modular mechanism to encapsulate (i) compositional changes to the host language, (ii) transformations to address various concerns such as compilation and highlighting, and (iii) scoping rules to control visibility of language extensions. We describe the design and implementation of language boxes, and show with the help of several examples how modular extensions can be introduced to a host language and environment.
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A new Swiss federal licencing examination for human medicine (FLE) was developed and released in 2011. This paper describes the process from concept design to the first results obtained on implementation of the new examination. The development process was based on the Federal Act on University Medical Professions and involved all national stakeholders in this venture. During this process questions relating to the assessment aims, the assessment formats, the assessment dimensions, the examination content and necessary trade-offs were clarified. The aims were to create a feasible, fair, valid and psychometrically sound examination in accordance with international standards, thereby indicating the expected knowledge and skills level at the end of undergraduate medical education. Finally, a centrally managed and locally administered examination comprising a written multiple-choice element and a practical “clinical skills” test in the objective structured clinical examination (OSCE) format was developed. The first two administrations of the new FLE show that the examination concept could be implemented as intended. The anticipated psychometric indices were achieved and the results support the validity of the examination. Possible changes to the format or content in the future are discussed.
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Liver transplantation recipients, like other solid organ transplantation recipients, have an increased risk of dermatologic problems due to their long-term immunosuppression and benefit from pre-and post-transplantation screenings, and management by a dermatologist and dermatologic care should be integrated into the comprehensive, multidisciplinary care of liver transplantation recipients [1,2]. Cutaneous findings include aesthetic alterations, infections, precancerous lesions, and malignancies. The severity of skin alterations ranges from benign, unpleasant changes to life-threatening conditions [3-5]. In addition to skin cancer diagnosis and management, visits with a dermatologist serve to educate and improve the patient's sun-protection behavior. Among all solid organ transplantations, liver transplantation requires the least amount of immunosuppression, sometimes even permitting its complete cessation [6]. As a result, patients who have undergone liver transplantation tend to have fewer dermatologic complications compared with other solid organ transplantation recipients [7]. However, due to the large volume of the liver, patients undergoing liver transplantation receive more donor lymphocytes than kidney, heart, or lung transplantation recipients. Because of the immunosuppression, the transplanted lymphocytes proliferate and rarely trigger graft-versus-host-disease [8,9]. This topic will provide an overview of dermatologic disorders that may be seen following liver transplantation. A detailed discussion of skin cancer following solid organ transplantation and the general management of patients following liver transplantation are discussed separately. (See "Development of malignancy following solid organ transplantation" and "Management of skin cancer in solid organ transplant recipients" and "Long-term management of adult liver transplant recipients".)
Developmental changes in sleep biology and potential effects on adolescent behavior and caffeine use
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Adolescent development includes changes in the biological regulatory processes for the timing of sleep. Circadian rhythm changes and changes to the sleep-pressure system (sleep homeostasis) during adolescence both favor later timing of sleep. These changes, combined with prevailing social pressures, are responsible for most teens sleeping too late and too little; those who sleep least report consuming more caffeine. Although direct research findings are scarce, the likelihood of use and abuse of caffeine-laden products grows across the adolescent years due, in part, to excessive sleepiness
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Grasslands provide many ecosystem services including carbon storage, biodiversity preservation and livestock forage production. These ecosystem services will change in the future in response to multiple global environmental changes, including climate change and increased nitrogen inputs. We conducted an experimental study over 3 years in a mesotrophic grassland ecosystem in southern England. We aimed to expose plots to rainfall manipulation that simulated IPCC 4th Assessment projections for 2100 (+15 % winter rainfall and −30 % summer rainfall) or ambient climate, achieving +15 % winter rainfall and −39 % summer rainfall in rainfall-manipulated plots. Nitrogen (40 kg ha−1 year−1) was also added to half of the experimental plots in factorial combination. Plant species composition and above ground biomass were not affected by rainfall in the first 2 years and the plant community did not respond to nitrogen enrichment throughout the experiment. In the third year, above-ground plant biomass declined in rainfall-manipulated plots, driven by a decline in the abundances of grass species characteristic of moist soils. Declining plant biomass was also associated with changes to arthropod communities, with lower abundances of plant-feeding Auchenorrhyncha and carnivorous Araneae indicating multi-trophic responses to rainfall manipulation. Plant and arthropod community composition and plant biomass responses to rainfall manipulation were not modified by nitrogen enrichment, which was not expected, but may have resulted from prior nitrogen saturation and/or phosphorus limitation. Overall, our study demonstrates that climate change may in future influence plant productivity and induce multi-trophic responses in grasslands.
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BACKGROUND Recovery after arterial ischaemic stroke is known to largely depend on the plastic properties of the brain. The present study examines changes in the network topography of the developing brain after stroke. Effects of brain damage are best assessed by examining entire networks rather than single sites of structural lesions. Relating these changes to post-stroke neuropsychological variables and motor abilities will improve understanding of functional plasticity after stroke. Inclusion of healthy controls will provide additional insight into children's normal brain development. Resting state functional magnetic resonance imaging is a valid approach to topographically investigate the reorganisation of functional networks after a brain lesion. Transcranial magnetic stimulation provides complementary output information. This study will investigate functional reorganisation after paediatric arterial ischaemic stroke by means of resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a cross-sectional plus longitudinal study design. The general aim of this study is to better understand neuroplasticity of the developing brain after stroke in order to develop more efficacious therapy and to improve the post-stroke functional outcome. METHODS The cross-sectional part of the study will investigate the functional cerebral networks of 35 children with chronic arterial ischaemic stroke (time of the lesion >2 years). In the longitudinal part, 15 children with acute arterial ischaemic stroke (shortly after the acute phase of the stroke) will be included and investigations will be performed 3 times within the subsequent 9 months. We will also recruit 50 healthy controls, matched for age and sex. The neuroimaging and neurophysiological data will be correlated with neuropsychological and neurological variables. DISCUSSION This study is the first to combine resting state functional magnetic resonance imaging and transcranial magnetic stimulation in a paediatric population diagnosed with arterial ischaemic stroke. Thus, this study has the potential to uniquely contribute to the understanding of neuronal plasticity in the brains of healthy children and those with acute or chronic brain injury. It is expected that the results will lead to the development of optimal interventions after arterial ischaemic stroke.
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Yakutia, Sakha Republic, in the Siberian Far East, represents one of the coldest places on Earth, with winter record temperatures dropping below -70 °C. Nevertheless, Yakutian horses survive all year round in the open air due to striking phenotypic adaptations, including compact body conformations, extremely hairy winter coats, and acute seasonal differences in metabolic activities. The evolutionary origins of Yakutian horses and the genetic basis of their adaptations remain, however, contentious. Here, we present the complete genomes of nine present-day Yakutian horses and two ancient specimens dating from the early 19th century and ∼5,200 y ago. By comparing these genomes with the genomes of two Late Pleistocene, 27 domesticated, and three wild Przewalski's horses, we find that contemporary Yakutian horses do not descend from the native horses that populated the region until the mid-Holocene, but were most likely introduced following the migration of the Yakut people a few centuries ago. Thus, they represent one of the fastest cases of adaptation to the extreme temperatures of the Arctic. We find cis-regulatory mutations to have contributed more than nonsynonymous changes to their adaptation, likely due to the comparatively limited standing variation within gene bodies at the time the population was founded. Genes involved in hair development, body size, and metabolic and hormone signaling pathways represent an essential part of the Yakutian horse adaptive genetic toolkit. Finally, we find evidence for convergent evolution with native human populations and woolly mammoths, suggesting that only a few evolutionary strategies are compatible with survival in extremely cold environments.