The rate of recovery in renal function when patients with HIV infection discontinue treatment with tenofovir

OBJECTIVES Tenofovir is associated with reduced renal function. It is not clear whether patients can be expected to fully recover their renal function if tenofovir is discontinued. METHODS We calculated the estimated glomerular filtration rate (eGFR) for patients in the Swiss HIV Cohort Study remaining on tenofovir for at least 1 year after starting a first antiretroviral therapy regimen with tenofovir and either efavirenz or the ritonavir-boosted protease inhibitor lopinavir, atazanavir or darunavir. We estimated the difference in eGFR slope between those who discontinued tenofovir after 1 year and those who remained on tenofovir. RESULTS A total of 1049 patients on tenofovir for at least 1 year were then followed for a median of 26 months, during which time 259 patients (25%) discontinued tenofovir. After 1 year on tenofovir, the difference in eGFR between those starting with efavirenz and those starting with lopinavir, atazanavir and darunavir was - 0.7 [95% confidence interval (CI) -2.3 to 0.8], -1.4 (95% CI -3.2 to 0.3) and 0.0 (95% CI -1.7 to 1.7) mL/min/1.73 m(2) , respectively. The estimated linear rate of decline in eGFR on tenofovir was -1.1 (95% CI -1.5 to -0.8) mL/min/1.73 m(2) per year and its recovery after discontinuing tenofovir was 2.1 (95% CI 1.3 to 2.9) mL/min/1.73 m(2) per year. Patients starting tenofovir with either lopinavir or atazanavir appeared to have the same rates of decline and recovery as those starting tenofovir with efavirenz. CONCLUSIONS If patients discontinue tenofovir, clinicians can expect renal function to recover more rapidly than it declined.

Impact of an abrupt cooling event on interglacial methane emissions in northern peatlands

Rapid changes in atmospheric methane (CH4), temperature and precipitation are documented by Greenland ice core data both for glacial times (the so called Dansgaard-Oeschger (D-O) events) as well as for a cooling event in the early Holocene (the 8.2 kyr event). The onsets of D-O warm events are paralleled by abrupt increases in CH4 by up to 250 ppb in a few decades. Vice versa, the 8.2 kyr event is accompanied by an intermittent decrease in CH4 of about 80 ppb over 150 yr. The abrupt CH4 changes are thought to mainly originate from source emission variations in tropical and boreal wet ecosystems, but complex process oriented bottom-up model estimates of the changes in these ecosystems during rapid climate changes are still missing. Here we present simulations of CH4 emissions from northern peatlands with the LPJ-Bern dynamic global vegetation model. The model represents CH4 production and oxidation in soils and transport by ebullition, through plant aerenchyma, and by diffusion. Parameters are tuned to represent site emission data as well as inversion-based estimates of northern wetland emissions. The model is forced with climate input data from freshwater hosing experiments using the NCAR CSM1.4 climate model to simulate an abrupt cooling event. A concentration reduction of ~10 ppb is simulated per degree K change of mean northern hemispheric surface temperature in peatlands. Peatland emissions are equally sensitive to both changes in temperature and in precipitation. If simulated changes are taken as an analogy to the 8.2 kyr event, boreal peatland emissions alone could only explain 23 of the 80 ppb decline in atmospheric methane concentration. This points to a significant contribution to source changes from low latitude and tropical wetlands to this event.

A virtual environment for the assessment and the rehabilitation of the visuo-constructional ability in dementia patients

This study proposes a VE that offers a reliable diagnosis of the stage of cognitive decline in dementia patients and assists the delay of this decline in terms of the visuo-constructional ability. The proposed VE, in the case of the assessment, presents a visuo-constructional completion task, which requires spatial perception, motor memory and the perception of the target object. In the case of the rehabilitation the VE uses sound as audio-feedback that, with the aid of the music perception, tends to develop an enhancement in the visuo-construction ability of the dementia patients that can be generalized even outside of the VE. The study examined 30 subjects that were normal controls (N), 30 patients suffering from memory disorders (Age-Associated Memory Impairment--AAMI) and 30 suffering from Alzheimer's Disease (AD). The results showed that there is a significant correlation between the performance in the visuo-constructional task and the dementia diagnosis. It also seems that the visuo-constructional ability of the (AD) patients can be statistically improved by the audio experience in the VE. The empirical results of this study offer an alternative diagnosis and treatment of dementia patients and could share some light in the brain sub-systems that are responsible for the visuo-constructional ability. Further studies are required in order to investigate the nature of this phenomenon more.

Archaeological silence and ecorefuges: arid events in the Puna of Atacama during the Middle Holocene

This paper briefly summarizes presearch concerning the mid-Holocene in the western slope of the puna de Atacama (20–25°S). Proxy data and dates from palynological, limnological, geomorphological archives were compared with data recovered from the archaeological sites in high altitude basins, intermediate ravines and piemontane paleowetlands. Due to exceptionally favorable conditions, numerous Early Holocene archaeological sites were found. In contrast, the lack of occupations in previously populated areas suggests a decline in human activity during the arid mid-Holocene. In this context, two key concepts are introduced: ecorefuge or ecological refuge, and archaeological silence (silencio arqueológico). The first refers to the particular favorable locations occupied by human groups during the mid-Holocene. The second provides a better understanding about the impact of the arid interval during this period on human adaptations in the most barren territories of the New World.

Regional differences in trait-like characteristics of the waking EEG in early adolescence

BACKGROUND The human waking EEG spectrum shows high heritability and stability and, despite maturational cortical changes, high test-retest reliability in children and teens. These phenomena have also been shown to be region specific. We examined the stability of the morphology of the wake EEG spectrum in children aged 11 to 13 years recorded over weekly intervals and assessed whether the waking EEG spectrum in children may also be trait-like. Three minutes of eyes open and three minutes of eyes closed waking EEG was recorded in 22 healthy children once a week for three consecutive weeks. Eyes open and closed EEG power density spectra were calculated for two central (C3LM and C4LM) and two occipital (O1LM and O2LM) derivations. A hierarchical cluster analysis was performed to determine whether the morphology of the waking EEG spectrum between 1 and 20 Hz is trait-like. We also examined the stability of the alpha peak using an ANOVA. RESULTS The morphology of the EEG spectrum recorded from central derivations was highly stable and unique to an individual (correctly classified in 85% of participants), while the EEG recorded from occipital derivations, while stable, was much less unique across individuals (correctly classified in 42% of participants). Furthermore, our analysis revealed an increase in alpha peak height concurrent with a decline in the frequency of the alpha peak across weeks for occipital derivations. No changes in either measure were observed in the central derivations. CONCLUSIONS Our results indicate that across weekly recordings, power spectra at central derivations exhibit more "trait-like" characteristics than occipital derivations. These results may be relevant for future studies searching for links between phenotypes, such as psychiatric diagnoses, and the underlying genes (i.e., endophenotypes) by suggesting that such studies should make use of more anterior rather than posterior EEG derivations.

Relations between adolescents' self-evaluations, time perspectives, motivation for school and their achievement in different countries and at different ages

The present study focused on the relations between the self-efficacy, social self-concept, time perspectives, school investment and academic achievement of students in four different European countries and in different adolescence periods. A total of 1623 students completed questionnaires. The relations between the concepts proved not to be specific to the Western or to the former Communist bloc countries studied. The expected general decline in investment and academic achievement over the adolescence period showed up in all four countries studied. Contrary to our hypothesis, however, this decline could not be explained by growing influences of either social self-concept or time perspectives regarding personal development on their investment. In fact, the effects of social self-concept were strongest for the youngest adolescence group. Students’ social self-concept was the best predictor for their investment, while self-efficacy proved to predict academic achievement best in all adolescence periods.

Metabolomics Reveals Aging-associated Attenuation of Noninvasive Radiation Biomarkers in Mice: Potential Role of Polyamine Catabolism and Incoherent DNA Damage-repair

Development of methods for rapid screening and stratification of subjects after exposure is an integral part of countermeasures against radiation. The potential demographic and exposure history-related heterogeneity of exposed populations warrants robust biomarkers that withstand and reflect such differences. In this study, the effect of aging and repeated exposure on the metabolic response to sublethal irradiation was examined in mice using UPLC-ESI-QTOF mass spectrometry. Aging attenuated postexposure elevation in excretions of DNA damage biomarkers as well as N(1)-acetylspermidine. Although N(1)-acetylspermidine and 2'-deoxyuridine elevation was highly correlated in all age groups, xanthine and N(1)-acetylspermidine elevation was poorly correlated in older mice. These results may reflect the established decline in DNA damage-repair efficiency associated with aging and indicate a novel role for polyamine metabolism in the process. Although repeated irradiation at long intervals did not affect the elevation of N(1)-acetylspermidine, 2'-deoxyuridine, and xanthine, it did significantly attenuate the elevation of 2'-deoxycytidine and thymidine compared to a single exposure. However, these biomarkers were found to identify exposed subjects with accuracy ranging from 82% (xanthosine) to 98% (2'-deoxyuridine), irrespective of their age and exposure history. This indicates that metabolic biomarkers can act as robust noninvasive signatures of sublethal radiation exposure.

Long-term perspective on wildfires in the western USA

Understanding the causes and consequences of wildfires in forests of the western United States requires integrated information about fire, climate changes, and human activity on multiple temporal scales. We use sedimentary charcoal accumulation rates to construct long-term variations in fire during the past 3,000 y in the American West and compare this record to independent fire-history data from historical records and fire scars. There has been a slight decline in burning over the past 3,000 y, with the lowest levels attained during the 20th century and during the Little Ice Age (LIA, ca. 1400-1700 CE Common Era]). Prominent peaks in forest fires occurred during the Medieval Climate Anomaly (ca. 950-1250 CE) and during the 1800s. Analysis of climate reconstructions beginning from 500 CE and population data show that temperature and drought predict changes in biomass burning up to the late 1800s CE. Since the late 1800s, human activities and the ecological effects of recent high fire activity caused a large, abrupt decline in burning similar to the LIA fire decline. Consequently, there is now a forest ``fire deficit'' in the western United States attributable to the combined effects of human activities, ecological, and climate changes. Large fires in the late 20th and 21st century fires have begun to address the fire deficit, but it is continuing to grow.

Practices of pediatric oncology and hematology providers regarding fertility issues: A European survey.

BACKGROUND Fertility is impaired in many survivors of childhood cancer following treatment. Preservation of fertility after cancer has become a central survivorship concern. Nevertheless, several doctors, patients, and families do not discuss fertility and recommendations for fertility preservation in pediatrics are still lacking. Recommendations based on scientific evidence are needed and before their development we wanted to assess the practice patterns of fertility preservation in Europe. PROCEDURES On behalf of the PanCare network, we sent a questionnaire to pediatric onco-hematology institutions across Europe. The survey consisted of 21 questions assessing their usual practices around fertility preservation. RESULTS One hundred ninety-eight institutional representatives across Europe received the survey and 68 (response rate 34.3%) responded. Pre-treatment fertility counseling was offered by 64 institutions. Counseling was done by a pediatric onco-hematologist in 52% (33/64) and in 32% (20/64) by a team. The majority of institutions (53%) lacked recommendations for fertility preservation. All 64 centers offered sperm banking; eight offered testicular tissue cryopreservation for pre-pubertal males. For females, the possibility of preserving ovarian tissue was offered by 40 institutions. CONCLUSIONS There is a high level of interest in fertility preservation among European centers responding to our survey. However, while most recommended sperm cryopreservation, many also recommended technologies whose efficacy has not been shown. There is an urgent need for evidence-based European recommendations for fertility preservation to help survivors deal with the stressful topic of fertility. Pediatr Blood Cancer 2014;9999:1-5. © 2014 Wiley Periodicals, Inc.

Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study.

BACKGROUND In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected. METHODS Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003-2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007-2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively. FINDINGS The proportion of PCV7 serotypes among all IPD cases (n=7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P<0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P=0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P=0.008), 19A (P=0.03) and 19F (P=0.005), compared to serotype 1 and 7F. CONCLUSION There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.

Estimating the Reproduction Number of Ebola Virus (EBOV) During the 2014 Outbreak in West Africa

The 2014 Ebola virus (EBOV) outbreak in West Africa is the largest outbreak of the genus Ebolavirus to date. To better understand the spread of infection in the affected countries, it is crucial to know the number of secondary cases generated by an infected index case in the absence and presence of control measures, i.e., the basic and effective reproduction number. In this study, I describe the EBOV epidemic using an SEIR (susceptible-exposed-infectious-recovered) model and fit the model to the most recent reported data of infected cases and deaths in Guinea, Sierra Leone and Liberia. The maximum likelihood estimates of the basic reproduction number are 1.51 (95% confidence interval [CI]: 1.50-1.52) for Guinea, 2.53 (95% CI: 2.41-2.67) for Sierra Leone and 1.59 (95% CI: 1.57-1.60) for Liberia. The model indicates that in Guinea and Sierra Leone the effective reproduction number might have dropped to around unity by the end of May and July 2014, respectively. In Liberia, however, the model estimates no decline in the effective reproduction number by end-August 2014. This suggests that control efforts in Liberia need to be improved substantially in order to stop the current outbreak.

Event-relating to potential dementia. Semantic processing in the course of healthy and pathological aging

While most healthy elderly are able to manage their everyday activities, studies showed that there are both stable and declining abilities during healthy aging. For example, there is evidence that semantic memory processes which involve controlled retrieval mechanism decrease, whereas the automatic functioning of the semantic network remains intact. In contrast, patients with Alzheimer’s disease (AD) suffer from episodic and semantic memory impairments aggravating their daily functioning. In AD, severe episodic as well as semantic memory deficits are observable. While the hallmark symptom of episodic memory decline in AD is well investigated, the underlying mechanisms of semantic memory deterioration remain unclear. By disentangling the semantic memory impairments in AD, the present thesis aimed to improve early diagnosis and to find a biomarker for dementia. To this end, a study on healthy aging and a study with dementia patients were conducted investigating automatic and controlled semantic word retrieval. Besides the inclusion of AD patients, a group of participants diagnosed with semantic dementia (SD) – showing isolated semantic memory loss – was assessed. Automatic and controlled semantic word retrieval was measured with standard neuropsychological tests and by means of event-related potentials (ERP) recorded during the performance of a semantic priming (SP) paradigm. Special focus was directed to the N400 or N400-LPC (late positive component) complex, an ERP that is sensitive to the semantic word retrieval. In both studies, data driven topographical analyses were applied. Furthermore, in the patient study, the combination of the individual baseline cerebral blood flow (CBF) with the N400 topography of each participant was employed in order to relate altered functional electrophysiology to the pathophysiology of dementia. Results of the aging study revealed that the automatic semantic word retrieval remains stable during healthy aging, the N400-LPC complex showed a comparable topography in contrast to the young participants. Both patient groups showed automatic SP to some extent, but strikingly the ERP topographies were altered compared to healthy controls. Most importantly, the N400 was identified as a putative marker for dementia. In particular, the degree of the topographical N400 similarity was demonstrated to separate healthy elderly from demented patients. Furthermore, the marker was significantly related to baseline CBF reduction in brain areas relevant for semantic word retrieval. Summing up, the first major finding of the present thesis was that all groups showed semantic priming, but that the N400 topography differed significantly between healthy and demented elderly. The second major contribution was the identification of the N400 similarity as a putative marker for dementia. To conclude, the present thesis added evidence of preserved automatic processing during healthy aging. Moreover, a possible marker which might contribute to an improved diagnosis and lead consequently to a more effective treatment of dementia was presented and has to be further developed.

Plant and arthropod community sensitivity to rainfall manipulation but not nitrogen enrichment in a successional grassland ecosystem

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.

Cessation and resuming of alglucosidase alfa in Pompe disease: a retrospective analysis.

Enzyme replacement therapy (ERT) with recombinant human alglucosidase alfa (rhGAA) in late-onset Pompe disease is moderately effective. Little is known about the clinical course after treatment termination and the resumption of ERT. In Switzerland, rhGAA therapy for Pompe disease was temporarily withdrawn after the federal court judged that the treatment costs were greatly out of proportion compared to the benefits. Re-treatment was initiated after the therapy was finally licensed. We retrospectively analysed seven Pompe patients, who underwent cessation and resumption of ERT (median age 43 years). The delay from first symptoms to final diagnosis ranged from 4 to 20 years. The demographics, clinical characteristics, assessments with the 6-min walking test (6-MWT), the predicted forced vital capacity (FVC) and muscle strength were analysed. Before initiation of ERT, all patients suffered from proximal muscle weakness of the lower limbs; one was wheelchair-bound and two patients received night-time non-invasive ventilation. Initial treatment stabilised respiratory function in most patients and improved their walking performance. After treatment cessation, upright FVC declined in most and the 6-MWT declined in all patients. Two patients needed additional non-invasive ventilatory support. Twelve months after resuming ERT, the respiratory and walking capacity improved again in most patients. However, aside for one patient, none of the patients reached the same level of respiratory function or distance walked in 6 min, as at the time of ERT withdrawal. We conclude that cessation of ERT in Pompe disease causes a decline in clinical function and should be avoided. Resuming treatment only partially recovers respiratory function and walking capacity.

BrainCheck - a very brief tool to detect incipient cognitive decline: optimized case-finding combining patient- and informant-based data.

INTRODUCTION Optimal identification of subtle cognitive impairment in the primary care setting requires a very brief tool combining (a) patients' subjective impairments, (b) cognitive testing, and (c) information from informants. The present study developed a new, very quick and easily administered case-finding tool combining these assessments ('BrainCheck') and tested the feasibility and validity of this instrument in two independent studies. METHODS We developed a case-finding tool comprised of patient-directed (a) questions about memory and depression and (b) clock drawing, and (c) the informant-directed 7-item version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Feasibility study: 52 general practitioners rated the feasibility and acceptance of the patient-directed tool. Validation study: An independent group of 288 Memory Clinic patients (mean ± SD age = 76.6 ± 7.9, education = 12.0 ± 2.6; 53.8% female) with diagnoses of mild cognitive impairment (n = 80), probable Alzheimer's disease (n = 185), or major depression (n = 23) and 126 demographically matched, cognitively healthy volunteer participants (age = 75.2 ± 8.8, education = 12.5 ± 2.7; 40% female) partook. All patient and healthy control participants were administered the patient-directed tool, and informants of 113 patient and 70 healthy control participants completed the very short IQCODE. RESULTS Feasibility study: General practitioners rated the patient-directed tool as highly feasible and acceptable. Validation study: A Classification and Regression Tree analysis generated an algorithm to categorize patient-directed data which resulted in a correct classification rate (CCR) of 81.2% (sensitivity = 83.0%, specificity = 79.4%). Critically, the CCR of the combined patient- and informant-directed instruments (BrainCheck) reached nearly 90% (that is 89.4%; sensitivity = 97.4%, specificity = 81.6%). CONCLUSION A new and very brief instrument for general practitioners, 'BrainCheck', combined three sources of information deemed critical for effective case-finding (that is, patients' subject impairments, cognitive testing, informant information) and resulted in a nearly 90% CCR. Thus, it provides a very efficient and valid tool to aid general practitioners in deciding whether patients with suspected cognitive impairments should be further evaluated or not ('watchful waiting').