Relationship between Contingent Negative Variation and afterimage duration in migraine patients.

Background: Abnormalities in electrocortical parameters and persistence of afterimage after visual stimulation are known to occur in migraine patients. The results of studies on Contingent Negative Variation (CNV) and afterimage persistence in migraine patients suggest a link between these two phenomena and a connection to the pathomechanism of migraine. Objectives: To date, no studies have investigated both afterimage duration and CNV parameters in the same subjects. The aim of this study was to investigate the relationship between the early component of CNV (iCNV) and the duration of the afterimage in migraine patients. Methods: Sixty seven migraine patients from the headache center of the University of Rostock Medical Center were examined for iCNV amplitude, iCNV habituation and afterimage duration. The subjects also completed questionnaires developed for this study and the MIDAS (Migraine Disability Assessment) questionnaire. Results: Associations were found between iCNV amplitude and afterimage duration and between habituation capacity and afterimage duration. A deficit in habituation capacity correlated with a significantly prolonged afterimage duration. Increased iCNV amplitude and prolonged afterimage duration were also significantly correlated. Conclusion: Conclusions about the pathophysiology of migraine can be drawn from the results of this study. The results support the hypothesis of cortical hyperexcitability as a consequence of a low pre-activation level, which may be a possible contributory cause of migraine. Furthermore, they allow assessment of whether the afterimage examination, which is easier and quicker to perform than the CNV examination, can be used as a diagnostic tool or as a parameter to monitor the course of therapy in people with migraine.

Effectiveness of a digitally supported care management programme to reduce unmet needs of family caregivers of people with dementia: study protocol for a cluster randomised controlled trial (GAIN).

BACKGROUND: Up to two-thirds of dementia care is provided by family caregivers who often experience high burden, little support and adverse health outcomes. Enabling and supporting family caregivers to provide care at home prevents early institutionalisation of the person with dementia and alleviates the economic burden of dementia in the long term. General practitioners (GPs), as the first point of contact, have a key role in identifying and managing burden and care needs of family caregivers. However, in routine care, this opportunity is often limited by time constraints and even if caregiver needs are recognised, detailed information about regionally available support and advice on healthcare services is often lacking. METHODS: This is a cluster randomised, controlled trial investigating the clinical use and cost-effectiveness of a digitally supported care management programme for caregivers of people with dementia (PwD). Five hundred family caregivers will be randomised at GP offices, specialist practices and memory clinics, with about n=250 participants per arm. Participants are eligible if they are the primary family caregiver of a PwD, are at least 18 years of age and provide informed consent. Participants in the intervention group will receive an individualised care management plan, which will be carried out by qualified study nurses in collaboration with the treating GP. All participants will receive a baseline assessment and a 6-months follow-up assessment. Participants in the wait-list control group will receive usual care. Starting at the 6 months' follow-up, the former controls will also receive an individualised management plan. Primary outcomes are the number of unmet needs (incl. the Camberwell Assessment of Need for the Elderly, CANE) and health-related quality of life (EQ-5D-5L) at 6 months. Secondary outcomes include caregiver burden (Zarit Burden Interview, ZBI), social support (Lubben Social Network Scale, LSNS), the use of medical and non-medical services (Questionnaire for the Use of Medical and Non-Medical Services, FIMA) and resource utilisation (Resource Utilisation in Dementia, RUD). The primary analysis will be based on intention-to-treat. Between- and within-group analyses and a cost-effectiveness analysis will be conducted to estimate the effect of the tablet PC-based care management programme. This trial is funded by the German Federal Joint Committee (G-BA) Innovation Fund. DISCUSSION: The findings of this trial will be useful in informing and improving current healthcare system structures and processes to support family dementia caregivers within routine care practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT04037501 . Registered on 30 July 2019.

Intersectoral care management for older people with cognitive impairment during and after hospital stays [intersec-CM]: study protocol for a process evaluation within a randomised controlled trial.

BACKGROUND: In the healthcare system in Germany, different institutions and actors play specific roles in the discharge and transition of patients from hospitals into primary care (Sachverständigenrat zur Begutachtung der Entwicklung im Gesundheitswesen, Wettbewerb an der Schnittstelle zwischen ambulanter und stationärer Gesundheitsversorgung, 2012). However, there are shortcomings in these intersectoral transitions. Especially in older people with cognitive impairment (PCI), discharge management often lacks coordination and cooperation between healthcare providers. This frequently results in higher rates of unscheduled readmission. The project intersec-CM is a randomised controlled trial (RCT) that aims to explore up to what extent an intersectoral care management (ICM) can improve this transition. This ICM is delivered by nurses with special training in care management. The objective of this paper is to describe a mixed-methods process evaluation of the intersectoral care management intervention and the factors that facilitate and inhibit its implementation. METHODS: Different study designs for process evaluations from previous literature were collected and analysed according to the dimension implementation fidelity, satisfaction with the intervention, feasible transfer into routine care, optimum point of time, frequency and execution of the intervention, and context factors. RESULTS: The actor-network theory was chosen as the theoretic framework for the process evaluation. Based on this theory, a mixed-methods design was developed to combine and integrate qualitative and quantitative evaluation methods. The qualitative part includes semi-structured interviews using topic guides (phase 1) and later in-depth interviews with narrative portions (phase 3), which will be analysed by using the qualitative content analysis according to Kuckartz. The quantitative survey (phase 2) is conducted with standardised questionnaires. DISCUSSION: Challenges in data collection include the development of interview guidelines, which require different terminologies depending on every specific actor targeted in the intervention. Conducting the interviews, there is a risk of misunderstanding the older PCI by the interviewer and vice versa. However, the combination of qualitative and quantitative approaches as different techniques of process evaluation may help to capture, integrate and analyse data on different dimensions of the intervention. CONCLUSIONS: The results of our process evaluation may serve as an implementation guideline for intersectoral care management in the German healthcare system. Furthermore, the approach to evaluate the process of a complex intervention in health care for older PCI may serve as a stimulus to broaden the evidence base also of other complex intervention studies to improve health care for this vulnerable group. The study was ethically approved by the Ethics Committee of the Ernst-Moritz-Arndt University of Greifswald. The study has been registered at the U.S. National Library of Medicine. TRIAL REGISTRATION: ClinicalTrials.gov NCT03359408 . Registered on 2 December 2017. The approximate date when recruitment to the process evaluation of the study will be completed is 31 May 2021.

Target and suspect screening analysis reveals persistent emerging organic contaminants in soils and sediments.

An approach to identifying persistent organic contaminants in the environment was developed and executed for Switzerland as an example of an industrialized country. First, samples were screened with an in-house list using liquid chromatography high-resolution mass spectrometry (LC-HRMS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) in 13 samples from the Swiss National Soil Monitoring Network and three sediment cores of an urban and agricultural contaminated lake. To capture a broader range of organic contaminants, the analysis was extended with a suspect screening analysis by LC-HRMS/MS of >500 halogenated compounds obtained from a Swiss database that includes industrial and household chemicals identified, by means of fugacity modeling, as persistent substances in the selected matrices. In total, the confirmation of 96 compounds with an overlap of 34 in soil and sediment was achieved. The identified compounds consist generally of esters, tertiary amines, trifluoromethyls, organophosphates, azoles and aromatic azines, with azoles and triazines being the most common groups. Newly identified compounds include transformation products, pharmaceuticals such as the flukicide niclofolan, the antimicrobial cloflucarban, and the fungicide mandipropamid. The results indicate that agricultural and urban soils as well as sediments impacted by agriculture and wastewater treatment plants (WWTPs) are the most contaminated sites. The plausibility of this outcome confirms the combination of chemical inventory, modeling of partitioning and persistence, and HRMS-based screening as a successful approach to shed light on less frequently or not yet investigated environmental contaminants and emphasizes the need for more soil and sediment monitoring in the future.

Why do family dementia caregivers reject caregiver support services? Analyzing types of rejection and associated health-impairments in a cluster-randomized controlled intervention trial.

BACKGROUND: Although there are a number of support services accessible for most family dementia caregivers, many caregivers reject available and affordable support. Previous research suggests that rejections of support services may result from insufficient fit of available services with caregivers' unmet needs and a lack of acknowledgement of caregivers' unmet needs and associated support services. The present study investigates (a) the number, proportion and types of caregivers' rejection on recommended tailored support, (b) socio-demographic and clinical determinants of caregiver's rejection of both people with dementia (PwD) and caregivers, and (c) caregivers' health-related variables related to caregivers' rejection. METHODS: Caregivers' rejection of tailored support services was identified based on a standardized, computerized unmet needs assessment conducted by dementia-specific qualified nurses. The present analysis is based on data of n = 226 dyads of caregivers and their community-dwelling PwD who participated in a general practitioner (GP)-based, cluster-randomized intervention trial. The trial was approved by the Ethical Committee of the Chamber of Physicians of Mecklenburg-Western Pomerania, registry number BB 20/11. Data analyses were conducted using Stata/IC 13.1. We conducted Welch's t-test, Pearson's product-moment correlation, and conditional negative binomial regression models with random effects for GP to account for over-dispersed count data. RESULTS: In sum, n = 505 unmet needs were identified and the same number of tailored recommendations were identified for n = 171 family dementia caregivers from the intervention group at baseline. For n = 55 family dementia caregivers not a single unmet need and recommendation were identified. A total of 17.6% (n = 89) of the recommendations were rejected by caregivers. Rejection rates of caregivers differed by type of recommendation. Whereas caregivers' rejection rate on recommendations concerning mental health (3.6%), physical health (2.5%), and social, legal, and financial affairs (0%) were low, caregivers' rejection rates concerning social integration (especially caregiver supporting groups) was high (71.7%). Thus, the rejections of family dementia caregivers are mainly linked to the delegation to caregiver supporting groups. Caregivers' rejections were mainly related to personal factors of caregivers (n = 66), service-related factors (n = 6), relational factors (n = 1), and other factors (n = 17). Furthermore, our results showed that the number of caregivers' rejections was associated with a higher functional status of the PwD and are mainly associated with the rejection of caregiver supporting groups. Thus, caregivers visit supporting groups more often when the PwD shows low abilities in activities of daily living. Importantly, this is independent of the status of cognition and depression of the PwD as well as the physical and mental health of the family dementia caregivers. CONCLUSIONS: Our results underline the importance of understanding factors that determine caregivers' rejection of support services. These need to be specifically addressed in tailored solutions for caregivers' support services. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01401582 (date: July 25, 2011, prospective registered).

Supporting elderly people with cognitive impairment during and after hospital stays with intersectoral care management: study protocol for a randomized controlled trial.

BACKGROUND: The sectorization of health-care systems leads to inefficient treatment, especially for elderly people with cognitive impairment. The transition from hospital care to primary care is insufficiently coordinated, and communication between health-care providers is often lacking. Consequences include a further deterioration of health, higher rates of hospital readmissions, and institutionalization. Models of collaborative care have shown their efficacy in primary care by improving patient-related outcomes. The main goal of this trial is to compare the effectiveness of a collaborative care model with usual care for people with cognitive impairment who have been admitted to a hospital for treatment due to a somatic illness. The aim of the intervention is to improve the continuity of treatment and care across the transition between the in-hospital and adjoining primary care sectors. METHODS/DESIGN: The trial is a longitudinal multisite randomized controlled trial with two arms (care as usual and intersectoral care management). Inclusion criteria at the time of hospital admission due to a somatic illness are age 70+ years, cognitive impairment (Mini Mental State Examination, MMSE ≤26), living at home, and written informed consent. Each participant will have a baseline assessment at the hospital and two follow-up assessments at home (3 and 12 months after discharge). The estimated sample size is n = 398 people with cognitive inmpairement plus their respective informal caregivers (where available). In the intersectoral care management group, specialized care managers will develop, implement, and monitor individualized treatment and care based on comprehensive assessments of the unmet needs of the patients and their informal caregivers. These assessments will occur at the hospital and in participants' homes. Primary outcomes are (1) activities of daily living, (2) readmission to the hospital, and (3) institutionalization. Secondary outcomes include (a) frailty, (b) delirium, (c) quality of life, (d) cognitive status, (e) behavioral and psychological symptoms of dementia, (f) utilization of services, and (g) informal caregiver burden. DISCUSSION: In the event of proving efficacy, this trial will deliver a proof of concept for implementation into routine care. The cost-effectiveness analyses as well as an independent process evaluation will increase the likelihood of meeting this goal. The trial will enable an in-depth analysis of mediating and moderating effects for different health outcomes at the interface between hospital care and primary care. By highlighting treatment and care, the study will provide insights into unmet needs at the time of hospital admission, and the opportunities and barriers to meeting those needs during the hospital stay and after discharge. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03359408 ; December 2, 2017.

Twenty-five years of observations of soil organic carbon in Swiss croplands showing stability overall but with some divergent trends.

The temporal evolution of soil organic carbon (SOC) is of major importance given its status as a key parameter in many soil functions. Furthermore, soils constitute an important reservoir of carbon in our environment. In light of climate change, consistent SOC data over extended periods in combination with information on agricultural management are much required, but still scarce. We report SOC changes in the topsoil (0-20 cm) of Swiss cropland measured at well-defined monitoring sites resampled every 5 years from 1990 to 2014 by the Swiss Soil Monitoring Network NABO using consistent sampling protocols and quality assurance. Data on agricultural management practices were retrieved from farmers. Overall, SOC remained stable for the ensemble of monitoring sites, although increasing and decreasing trends were observed for individual sites, ranging from - 11 to + 16% relative change per decade. Changes in the agricultural management of cropland triggered substantial changes in SOC contents for some sites. Moreover, sites with a low ratio of SOC/clay (< 0.1) generally showed more positive trends than sites with higher ratios. We presume that SOC was either at or near steady state, given the consistency of management practices over the last few decades. Finally, our study provides insights into the uncertainties related to (real-world) SOC monitoring and underlines the relevance of short-term SOC variations that could hamper the detection of long-term trends. The minimum detectable change (MDC) by the applied monitoring scheme is estimated at 0.35% per year, in relative terms.

The Fate of Zn in Agricultural Soils: A Stable Isotope Approach to Anthropogenic Impact, Soil Formation, and Soil-Plant Cycling.

The supplementation of Zn to farm animal feed and the excretion via manure leads to an unintended Zn input to agricultural systems, which might compromise the long-term soil fertility. The Zn fluxes at three grassland sites in Switzerland were determined by a detailed analysis of relevant inputs (atmospheric deposition, manure, weathering) and outputs (seepage water, biomass harvest) during one hydrological year. The most important Zn input occurred through animal manure (1076-1857 g ha-1 yr-1) and Zn mass balances revealed net Zn accumulations (456-1478 g ha-1 yr-1). We used Zn stable isotopes to assess the importance of anthropogenic impacts and natural long-term processes on the Zn distribution in soils. Soil-plant cycling and parent material weathering were identified as the most important processes, over the entire period of soil formation (13 700 years), whereas the soil pH strongly affected the direction of Zn isotopic fractionation. Recent anthropogenic inputs of Zn only had a smaller influence compared to the natural processes of the past 13 700 years. However, this will probably change in the future, as Zn stocks in the 0-20 cm layer will increase by 22-68% in the next 100 years, if Zn inputs remain on the same level as today.

Using isotopes to trace freshly applied cadmium through mineral phosphorus fertilization in soil-fertilizer-plant systems.

Applications of mineral phosphorus (P) fertilizer can lead to cadmium (Cd) accumulation in soils and can increase Cd concentrations in edible crop parts. To determine the fate of freshly applied Cd, a Cd source tracing experiment was conducted in three soil-fertilizer-wheat systems by using a mineral P fertilizer labeled with the radio isotope 109Cd and by exploiting natural differences in Cd stable isotope compositions (δ114/110Cd). Source tracing with stable isotopes overestimated the proportion of Cd in plants derived from the P fertilizer, because the isotope ratios of the sources were not sufficiently distinct from those of the soils. Despite indistinguishable extractable Cd pools between control and treatments, the addition of P fertilizer resulted in a more negative apparent isotope fractionation between soil and wheat. Overall, the radio isotope approach provided more robust results and revealed that 6.5 to 15% of the Cd in the shoot derived from the fertilizer. From the introduced Cd, a maximum of 2.2% reached the wheat shoots, whilst 97.8% remained in the roots and soils. The low recoveries of the fertilizer derived Cd suggest that continuous P fertilizer application in the past decades can lead to a build-up of a residual Cd pool in soils.

Towards an understanding of the Cd isotope fractionation during transfer from the soil to the cereal grain.

Cd in soils might be taken up by plants, enter the food chain and endanger human health. This study investigates the isotopic fractionation of major processes during the Cd transfer from soils to cereal grains. Thereto, soil, soil solution, wheat and barley plants (roots, straw and grains) were sampled in the field at three study sites during two vegetation periods. Cd concentrations and δ114/110Cd values were determined in all samples. The composition of the soil solution was analyzed and the speciation of the dissolved Cd was modelled. Isotopic fractionation between soils and soil solutions (Δ114/110Cd20-50cm-soil solution = -0.61 to -0.68‰) was nearly constant among the three soils. Cd isotope compositions in plants were heavier than in soils (Δ114/110Cd0-20cm-plants = -0.55 to -0.31‰) but lighter than in soil solutions (Δ114/110Cdsoil solution-plants = 0.06-0.36‰) and these differences correlated with Cd plant-uptake rates. In a conceptual model, desorption from soil, soil solution speciation, adsorption on root surfaces, diffusion, and plant uptake were identified as the responsible processes for the Cd isotope fractionation between soil, soil solution and plants whereas the first two processes dominated over the last three processes. Within plants, compartments with lower Cd concentrations were enriched in light isotopes which might be a consequence of Cd retention mechanisms, following a Rayleigh fractionation, in which barley cultivars were more efficient than wheat cultivars.

Identifying Unmet Needs of Family Dementia Caregivers: Results of the Baseline Assessment of a Cluster-Randomized Controlled Intervention Trial.

BACKGROUND: Caregivers providing informal care for people with dementia (PwD) often report unmet needs, burden, and health impairments. Optimal support for family dementia caregivers will likely benefit from better understanding and assessment of the prevalence and types of caregivers' unmet needs and associated socio-demographic and clinical characteristics. OBJECTIVE: The present study investigates 1) the number and types of caregivers' unmet needs, 2) socio-demographic and clinical characteristics of both PwD and caregivers, and 3) caregivers' burden and health-related outcomes that are related to caregivers' unmet needs. METHODS: The present analyses are based on cross-sectional data of n = 226 dyads of caregivers and their community-dwelling PwD participating in a comprehensive standardized, computer-based caregivers' needs assessment within a general practitioner (GP)-based, cluster-randomized intervention trial. RESULTS: A total of n = 505 unmet needs were identified for n = 171 caregivers from the intervention group at baseline. Only 24.3% caregivers reported no unmet need (n = 55), whereas 75.7% caregivers had at least one unmet need (n = 171). Caregivers had on average 2.19 unmet needs (mean = 2.19, SD = 2.15). Specifically, 53.1% of caregivers had one up to three unmet needs (n = 120), 18.6% (n = 42) had three up to six unmet needs, and 4.0% (n = 9) had more than six unmet needs. DISCUSSION: Our results underline the importance of a comprehensive needs assessment for family dementia caregivers to develop and implement concepts that can provide family dementia caregivers with optimal support.

P2Y1 receptor blockade normalizes network dysfunction and cognition in an Alzheimer's disease model.

Astrocytic hyperactivity is an important contributor to neuronal-glial network dysfunction in Alzheimer's disease (AD). We have previously shown that astrocyte hyperactivity is mediated by signaling through the P2Y1 purinoreceptor (P2Y1R) pathway. Using the APPPS1 mouse model of AD, we here find that chronic intracerebroventricular infusion of P2Y1R inhibitors normalizes astroglial and neuronal network dysfunction, as measured by in vivo two-photon microscopy, augments structural synaptic integrity, and preserves hippocampal long-term potentiation. These effects occur independently from ß-amyloid metabolism or plaque burden but are associated with a higher morphological complexity of periplaque reactive astrocytes, as well as reduced dystrophic neurite burden and greater plaque compaction. Importantly, APPPS1 mice chronically treated with P2Y1R antagonists, as well as APPPS1 mice carrying an astrocyte-specific genetic deletion (Ip3r2-/-) of signaling pathways downstream of P2Y1R activation, are protected from the decline of spatial learning and memory. In summary, our study establishes the restoration of network homoeostasis by P2Y1R inhibition as a novel treatment target in AD.

Zinc isotope fractionation during grain filling of wheat and a comparison of zinc and cadmium isotope ratios in identical soil-plant systems.

Remobilization of zinc (Zn) from shoot to grain contributes significantly to Zn grain concentrations and thereby to food quality. On the other hand, strong accumulation of cadmium (Cd) in grain is detrimental for food quality. Zinc concentrations and isotope ratios were measured in wheat shoots (Triticum aestivum) at different growth stages to elucidate Zn pathways and processes in the shoot during grain filling. Zinc mass significantly decreased while heavy Zn isotopes accumulated in straw during grain filling (Δ66 Znfull maturity-flowering  = 0.21-0.31‰). Three quarters of the Zn mass in the shoot moved to the grains, which were enriched in light Zn isotopes relative to the straw (Δ66 Zngrain-straw -0.21 to -0.31‰). Light Zn isotopes accumulated in phloem sinks while heavy isotopes were retained in phloem sources likely because of apoplastic retention and compartmentalization. Unlike for Zn, an accumulation of heavy Cd isotopes in grains has previously been shown. The opposing isotope fractionation of Zn and Cd might be caused by distinct affinities of Zn and Cd to oxygen, nitrogen, and sulfur ligands. Thus, combined Zn and Cd isotope analysis provides a novel tool to study biochemical processes that separate these elements in plants.

Fate of Cd in Agricultural Soils: A Stable Isotope Approach to Anthropogenic Impact, Soil Formation, and Soil-Plant Cycling.

The application of mineral phosphate (P) fertilizers leads to an unintended Cd input into agricultural systems, which might affect soil fertility and quality of crops. The Cd fluxes at three arable sites in Switzerland were determined by a detailed analysis of all inputs (atmospheric deposition, mineral P fertilizers, manure, and weathering) and outputs (seepage water, wheat and barley harvest) during one hydrological year. The most important inputs were mineral P fertilizers (0.49 to 0.57 g Cd ha-1 yr-1) and manure (0.20 to 0.91 g Cd ha-1 yr-1). Mass balances revealed net Cd losses for cultivation of wheat (-0.01 to -0.49 g Cd ha-1 yr-1) but net accumulations for that of barley (+0.18 to +0.71 g Cd ha-1 yr-1). To trace Cd sources and redistribution processes in the soils, we used natural variations in the Cd stable isotope compositions. Cadmium in seepage water (δ114/110Cd = 0.39 to 0.79‰) and plant harvest (0.27 to 0.94‰) was isotopically heavier than in soil (-0.21 to 0.14‰). Consequently, parent material weathering shifted bulk soil isotope compositions to lighter signals following a Rayleigh fractionation process (ε ≈ 0.16). Furthermore, soil-plant cycling extracted isotopically heavy Cd from the subsoil and moved it to the topsoil. These long-term processes and not anthropogenic inputs determined the Cd distribution in our soils.

Long-Term Persistence of Pesticides and TPs in Archived Agricultural Soil Samples and Comparison with Pesticide Application.

For polar and more degradable pesticides, not many data on long-term persistence in soil under field conditions and real application practices exist. To assess the persistence of pesticides in soil, a multiple-compound screening method (log Kow 1.7-5.5) was developed based on pressurized liquid extraction, QuEChERS and LC-HRMS. The method was applied to study 80 polar pesticides and >90 transformation products (TPs) in archived topsoil samples from the Swiss Soil Monitoring Network (NABO) from 1995 to 2008 with known pesticide application patterns. The results reveal large variations between crop type and field sites. For the majority of the sites 10-15 pesticides were identified with a detection rate of 45% at concentrations between 1 and 330 µg/kgdw in soil. Furthermore, TPs were detected in 47% of the cases where the "parent-compound" was applied. Overall, residues of about 80% of all applied pesticides could be detected with half of these found as TPs with a persistence of more than a decade.

Polycyclic aromatic hydrocarbons and polychlorinated biphenyls in soils of Mayabeque, Cuba.

Cuba is a country in transition with a considerable potential for economic growth. Soils are recipients and integrators of chemical pollution, a frequent negative side effect of increasing industrial activities. Therefore, we established a soil monitoring network to monitor polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs) in soils of Mayabeque, a Cuban province southeast of Havana. Concentrations of the sum of the 16 US EPA PAHs and of the seven IRMM PCBs in soils from 39 locations ranged from 20 to 106 µg kg-1 and from 1.1 to 7.6 µg kg-1, respectively. While such concentrations can be considered as low overall, they were in several cases correlated with the distance of sampling sites to presumed major emission sources, with some of the concomitantly investigated source diagnostic PAH ratios, and with black carbon content. The presented data adds to the limited information on soil pollution in the Caribbean region and serves as a reference time point before the onset of a possible further industrial development in Cuba. It also forms the basis to set up and adapt national environmental standards.

Accumulation of cadmium and uranium in arable soils in Switzerland.

Mineral phosphorus (P) fertilizers contain contaminants that are potentially hazardous to humans and the environment. Frequent mineral P fertilizer applications can cause heavy metals to accumulate and reach undesirable concentrations in agricultural soils. There is particular concern about Cadmium (Cd) and Uranium (U) accumulation because these metals are toxic and can endanger soil fertility, leach into groundwater, and be taken up by crops. We determined total Cd and U concentrations in more than 400 topsoil and subsoil samples obtained from 216 agricultural sites across Switzerland. We also investigated temporal changes in Cd and U concentrations since 1985 in soil at six selected Swiss national soil monitoring network sites. The mean U concentrations were 16% higher in arable topsoil than in grassland topsoil. The Cd concentrations in arable and grassland soils did not differ, which we attribute to soil management practices and Cd sources other than mineral P fertilizers masking Cd inputs from mineral P fertilizers. The mean Cd and U concentrations were 58% and 9% higher, respectively, in arable topsoil than in arable subsoil, indicating that significant Cd and U inputs to arable soils occurred in the past. Geochemical mass balances confirmed this, indicating an accumulation of 52% for Cd and 6% for U. Only minor temporal changes were found in the Cd concentrations in topsoil from the six soil-monitoring sites, but U concentrations in topsoil from three sites had significantly increased since 1985. Sewage sludge and atmospheric deposition were previously important sources of Cd to agricultural soils, but today mineral P fertilizers are the dominant sources of Cd and U. Future Cd and U inputs to agricultural soils may be reduced by using optimized management practices, establishing U threshold values for mineral P fertilizers and soils, effectively enforcing threshold values, and developing and using clean recycled P fertilizers.

Preclinical evaluation of a diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy in a non-Hodgkin lymphoma mouse model.

Radioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy ß-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma. Even at high doses of 16 MBq this diabody RIC was well tolerated by NOD Rag1(null) IL2rγ(null) (NRG) mice and did not reveal signs of organ long-term toxicity 80 days post injection. Combination therapy of the diabody RIC with unconjugated anti-CD20 Rituximab demonstrated therapeutic efficacy in established disseminated mantle cell lymphoma xenograft models. When compared with the combination of the IgG formatted (177)Lu anti-CD22 antibody and Rituximab, dual targeted therapy with the diabody RIC achieved an improved reduction of disease burden in the first nine days following treatment. The data indicate that the PEGylated anti-CD22 diabody may have potential for extending the repertoire of radiopharmaceuticals for the treatment of patients with B-NHL.

Cadmium Isotope Fractionation in Soil-Wheat Systems.

Analyses of stable metal isotope ratios constitute a novel tool in order to improve our understanding of biogeochemical processes in soil-plant systems. In this study, we used such measurements to assess Cd uptake and transport in wheat grown on three agricultural soils under controlled conditions. Isotope ratios of Cd were determined in the bulk C and A horizons, in the Ca(NO3)2-extractable Cd soil pool, and in roots, straw, and grains. The Ca(NO3)2-extractable Cd was isotopically heavier than the Cd in the bulk A horizon (Δ(114/110)Cdextract-Ahorizon = 0.16 to 0.45‰). The wheat plants were slightly enriched in light isotopes relative to the Ca(NO3)2-extractable Cd or showed no significant difference (Δ(114/110)Cdwheat-extract = -0.21 to 0.03‰). Among the plant parts, Cd isotopes were markedly fractionated: straw was isotopically heavier than roots (Δ(114/110)Cdstraw-root = 0.21 to 0.41‰), and grains were heavier than straw (Δ(114/110)Cdgrain-straw = 0.10 to 0.51‰). We suggest that the enrichment of heavy isotopes in the wheat grains was caused by mechanisms avoiding the accumulation of Cd in grains, such as the chelation of light Cd isotopes by thiol-containing peptides in roots and straw. These results demonstrate that Cd isotopes are significantly and systematically fractionated in soil-wheat systems, and the fractionation patterns provide information on the biogeochemical processes in these systems.