Effectiveness of ferritin-guided donation intervals in whole-blood donors in the Netherlands (FIND'EM): a stepped-wedge cluster-randomised trial.

BACKGROUND: Whole-blood donors are at increased risk for iron deficiency and anaemia. The current standard of haemoglobin monitoring is insufficient to ensure the maintenance of proper iron reserves and donor health. We aimed to determine the effects of ferritin-guided donation intervals for blood donor health and blood supply in the Netherlands. METHODS: In this stepped-wedge cluster-randomised trial (FIND'EM), the 138 fixed and mobile donation centres in the Netherlands are organised into 29 geographical clusters and the clusters were randomly assigned to four treatment groups, with two groups being further split into two per a protocol amendment. Eligible donors were whole-blood donors who consented for use of their leftover material in the study. Each group was sequentially crossed over from the existing policy (haemoglobin-based screening; control) to a ferritin-guided donation interval policy over a 3-year period. In the intervention groups, in addition to the existing haemoglobin screening, ferritin was measured in all new donors and at every fifth donation in repeat donors. Subsequent donation intervals were extended to 6 months if ferritin concentrations were 15-30 ng/mL and to 12 months if they were less than 15 ng/mL. Outcomes were measured cross-sectionally across all donation centres at four timepoints. Primary outcomes were ferritin and haemoglobin concentrations, iron deficiency, and haemoglobin-based deferrals. We assessed all outcomes by sex and menopausal status and significance for primary outcomes was indicated by a p value of less than 0·0125. This trial is registered in the Dutch trial registry, NTR6738, and is complete. FINDINGS: Between Sept 11, 2017, and Nov 27, 2020, 412 888 whole-blood donors visited a donation centre, and we did measurements on samples from 37 621 donations from 36 099 donors. Over 38 months, ferritin-guided donation intervals increased mean ferritin concentrations (by 0·18 log10 ng/mL [95% CI 0·15-0·22; p<0·0001] in male donors, 0·10 log10 ng/mL [0·06-0·15; p<0·0001] in premenopausal female donors, and 0·17 log10 ng/mL [0·12-0·21; p<0·0001] in postmenopausal female donors) and mean haemoglobin concentrations (by 0·30 g/dL [95% CI 0·22-0·38; p<0·0001] in male donors, 0·12 g/dL [0·03-0·20; p<0·0074] in premenopausal female donors, and 0·16 g/dL [0·05-0·27; p<0·0044] in postmenopausal female donors). Iron deficiency decreased by 36-38 months (odds ratio [OR] 0·24 [95% CI 0·18-0·31; p<0·0001] for male donors, 0·49 [0·37-0·64; p<0·0001] for premenopausal female donors, and 0·24 [0·15-0·37; p<0·0001] for postmenopausal female donors). At 36-38 months, haemoglobin-based deferral decreased significantly in male donors (OR at 36-38 months 0·21 [95% CI 0·10-0·40, p<0·0001]) but not significantly in premenopausal or postmenopausal female donors (0·81 [0·54-1·20; p=0·29] and 0·50 [95% CI 0·25-0·98; p=0·051], respectively). INTERPRETATION: Ferritin-guided donation intervals significantly improved haemoglobin and ferritin concentrations and significantly decreased iron deficiency over the study period. Haemoglobin-based deferrals decreased significantly for male donors, but not female donors. Although this intervention is overall beneficial for maintenance of iron and haemoglobin concentrations in donors, increased efforts are needed to recruit and retain donors. FUNDING: The Sanquin Research Programming Committee.

Blood safety markers in Dutch donors after relaxation of deferral for men who have sex with men: re-emergence of syphilis and HIV pre-exposure prophylaxis use.

BACKGROUND: Less discriminatory donor selection policies for men who have sex with men (MSM) may impact transfusion safety in terms of higher residual risks for known transfusion-transmitted infections (TTIs), increased vulnerability toward new TTIs that are also transmitted via sex, and HIV infections masked by pre-exposure prophylaxis (PrEP). STUDY DESIGN AND METHODS: TTI trends in Dutch donors were studied over a 13-year period (2011-2023), characterized by successive relaxations of MSM deferral criteria. Structured posttest counseling was performed to determine risk factors in TTI-positive donors. PrEP drug levels were measured in 9977 donations from male donors living in urban areas and in 67 donors with active or resolved syphilis. RESULTS: HIV incidence (from 5.8 to 1.5 per 1,000,000 donor years (DY)) and HBV incidence (from 12.4 to 4.5 per 1,000,000 DY) in Dutch donors decreased with less stringent MSM deferral criteria, while syphilis prevalence (from 26.4 to 44.1 per 100,000 new donors) and syphilis incidence (from 18.3 to 46.3 per 1,000,000 DY) increased over time. The proportion of MSM-related syphilis rose from 2% to 32% in new donors and from 12% to 27% in repeat donors. PrEP was detected in 2 of 9977 (0.02%) donations from male donors living in urban areas, and in 1 of 39 (2.6%) male donors with syphilis. DISCUSSION: To date, phasing out donor deferral for MSM had no significant impact on transfusion safety in the Netherlands. However, rising syphilis rates and (recent) PrEP use in the blood donor population, albeit rare, suggest an influx of donors with higher sexual risk profiles and requires intensified TTI surveillance in donors.

Iron supplementation: A qualitative study on the perception of blood donors, blood collection staff and donor physicians.

BACKGROUND AND OBJECTIVES: Iron supplementation is an effective strategy to mitigate donation-induced iron deficiency in blood donors. However, evidence on the perception of individuals involved in blood donation on iron supplementation as a blood service policy is lacking. This study aimed to evaluate the knowledge and perception of whole blood donors (donors), blood collection staff (collection staff) and donor physicians (physicians) regarding donation-induced iron loss and iron supplementation. MATERIALS AND METHODS: Online focus group discussions had four to six participants and followed a structured questioning approach. All participants had to be fluent in Dutch to participate, and donors had donated at least five times. Sixteen donors, eight collection staff members and four physicians participated in this study. Recordings were transcribed, coded and analysed using a grounded theory approach. RESULTS: Awareness of donation-induced iron loss was limited in donors. Donors and physicians were predominantly positive towards iron supplementation; the primary motivator for donors was to prevent deferral and reduce iron-deficiency-related symptoms. Improving donor health was the main argument for physicians to advocate iron supplementation. Staff had a critical view on iron supplementation as a policy, as they perceived it as unethical and possibly ineffective. A knowledge gap might underlie their concerns. CONCLUSION: Most individuals involved in blood donation are positive towards iron supplementation as a blood service policy. If implemented, guidance and monitoring is desired and adequate education of all stakeholders is required.

Increasing the upper age limit for blood donation: Perspectives from older donors.

BACKGROUND AND OBJECTIVES: In the Netherlands, as of April 2018, the upper age limit for blood donation has been raised from 69 to 79 years, providing an opportunity to study older donors' perspectives regarding donating at older age. This study aims to explore whether older donors agree with the increase of the age limit, if they feel obliged to continue donating, to identify their motivators and barriers for donating blood and describe donation-related experiences and complications. MATERIALS AND METHODS: An online survey was distributed among Dutch blood donors aged 68-73 years. The survey contained questions regarding the increase of the upper age limit, motivations and barriers for donating, donation-related experiences and obligatory feelings to continue donating. RESULTS: Six hundred sixty donors (55%) were included in the analyses, including 38 stopped donors. Most donors (92%) agreed with the increase of the upper age limit. Approximately 63% of participating donors felt obliged to continue donating, especially women with high education. Donors indicated they felt healthy enough to keep donating (95%), and 72% thought it is good for their health to keep donating. Few donors reported that they found it hard to keep donating (5%) or indicated that they did not feel healthy enough to donate or thought it was not safe for them anymore (3.4%). CONCLUSION: Most of the older donors agree with the increase of the upper age limit for blood donation, report only few and minor donation-related experiences or complications and are highly motivated to continue their donor career at an older age.

Donor knowledge and perceptions regarding donation-induced iron depletion and iron supplementation as a blood service policy.

BACKGROUND AND OBJECTIVES: Regular whole blood donations are associated with an increased risk of iron deficiency. Iron supplementation is an effective strategy to prevent donation-induced iron deficiency. However, research on donor perceptions towards such a policy is limited. Therefore, we aim to evaluate donors' knowledge on donation-induced iron depletion and their perceptions regarding iron supplementation as a blood service policy. MATERIALS AND METHODS: Three thousand Dutch whole blood donors were invited to complete a survey assessing their knowledge of donation-induced iron depletion and attitudes and perceptions towards iron supplementation as a policy. Linear regression modelling was used to evaluate associations between explanatory variables and perceptions. RESULTS: In total, 1093 (77.1%) donors were included in the analysis. Donors had poor knowledge of current iron management policies, but a better understanding of iron metabolism and supplementation. Iron supplementation as a policy was perceived mainly positive by donors, and the majority were willing to use iron supplements if provided. Iron supplementation was not perceived as invasive or negatively affecting donors' motivation to continue donating. Additional iron monitoring, information and donor physician involvement were regarded as important conditions for implementation. Male sex, trust in the blood service, prior experience with iron supplements and openness towards dietary supplements were strongly positively associated with willingness to use iron supplementation. CONCLUSION: Donors' knowledge regarding donation-induced iron depletion is limited, but not associated with their perceptions regarding iron supplementation. Donors do not consider iron supplementation as invasive, deterring or demotivating, and a majority are willing to take supplements if offered.

Whole blood donors' post-donation symptoms diminish quickly but are discouraging: Results from 6-day symptom diaries.

BACKGROUND: Whole blood donors may experience post-donation symptoms such as fatigue, dizziness, or headache after blood donation, which could influence donor retention. We aimed to examine post-donation symptoms during 1 week after whole blood donation, investigate donor characteristics associated with symptoms, and evaluate associations between symptoms and donor return. METHODS: During 1 week, whole blood donors who donated successfully at one of the collection centers in The Netherlands were invited to participate. Three thousand seventy six donors filled in a diary, assessing post-donation symptoms during days 1 to 6 after donation. We used linear mixed models analyses to determine the change in post-donation symptoms after donation for male and female donors separately. Furthermore, we investigated associations between post-donation symptoms and donors' physical characteristics using multivariable regression and determined associations between symptoms and donor return. RESULTS: Donors reported fatigue as the most common symptom, with approximately 3% of donors experiencing severe problems at the first day after donation. Multiple symptoms improved significantly up to day 3 after whole blood donation. Age, BMI, blood pressure (male donors), and blood volume (female donors) were significantly associated with post-donation symptoms. Donors with less fatigue after whole blood donation were more likely to return for their next donation within 31 days after receiving an invitation. CONCLUSION: Post-symptoms improve up to 3 days after whole blood donation. Our results may help blood collection centers to identify donors more prone to post-donation symptoms and provide personalized information about the presence and course of post-donation symptoms, possibly increasing donor return rates.

New blood donors in times of crisis: Increased donation willingness, particularly among people at high risk for attracting SARS-CoV-2.

BACKGROUND: Traditionally, during crises the number of new blood donors increases. However, the current coronavirus disease 2019 (COVID-19) pandemic created additional barriers to donate due to governmental prevention measures and increased personal health risks. In this report, we examined how the pandemic affected new donor registrations in the Netherlands, especially among groups with higher risk profiles for severe COVID-19. Additionally, we explored the role of media for blood donation and new donor registrations. STUDY DESIGN AND METHODS: We analyzed new donor registrations and attention for blood donation in newspapers and on social media from January until May 2020, in comparison to the same period in 2017 to 2019. RESULTS: After the introduction of nationwide prevention measures, several peaks in new donor registrations occurred, which coincided with peaks in media attention. Interestingly, people with a higher risk profile for COVID-19 (e.g., due to age or region of residence) were overrepresented among new registrants. DISCUSSION: In sum, the first peak of the current pandemic has led to increased new blood donor registrations, despite the associated increased health risks. Time and future studies will have to tell whether these new donors are one-off 'pandemic' donors or if they will become regular, loyal donors.

Host traits, lifestyle and environment are associated with human skin bacteria.

BACKGROUND: The human skin offers diverse ecosystems for microbial symbionts. However, the factors shaping skin-microbiome interactions are still insufficiently characterized. This contrasts with the broader knowledge about factors influencing gut microbiota. OBJECTIVES: We aimed to investigate major patterns of association of host traits, lifestyle and environmental factors with skin bacteria in two German populations. METHODS: This is a cross-sectional study with 647 participants from two population-based German cohorts, PopGen (n = 294) and KORA FF4 (n = 353), totalling 1794 skin samples. The V1-V2 regions of the 16S ribosomal RNA (rRNA) gene were sequenced. Associations were tested with two bacterial levels, community (beta diversity) and 16S rRNA gene amplicon sequence variants (ASVs). RESULTS: We validated known associations of the skin microbiota with skin microenvironment, age, body mass index and sex. These factors were associated with beta diversity and abundance of ASVs in PopGen, which was largely replicated in KORA FF4. Most intriguingly, dietary macronutrients and total dietary energy were associated with several ASVs. ASVs were also associated with smoking, alcohol consumption, skin pH, skin type, transepidermal water loss, education and several environmental exposures, including hours spent outdoors. Associated ASVs included members of the genera Propionibacterium, Corynebacterium and Staphylococcus. CONCLUSIONS: We expand the current understanding of factors associated with the skin bacterial community. We show the association of diet with skin bacteria. Finally, we hypothesize that the skin microenvironment and host physiology would shape the skin bacterial community to a greater extent compared with a single skin physiological feature, lifestyle and environmental exposure.

[ATLS® and TDSC®: how it fits together : A treatment concept for mass casualty and terrorist-related mass casualty situations, life-threatening and special scenarios]. / ATLS® und TDSC®: How it fits together : Ein Behandlungskonzept für MANV und TerrorMANV, lebensbedrohliche oder besondere Lagen.

Terrorist-related mass casualty incidents represent a medical and organizational challenge for all hospitals. The main reasons are the special patterns of injuries, the onset and development of the scenario, the lack of information at the beginning, the overall number of casualties and the number of uninjured but involved patients presenting at the hospital.Due to these circumstances and the high percentage of penetrating injuries with a permanent risk of uncontrollable bleeding and other life-threatening complications, a strategic and tactical initial surgical care is necessary.For these special terrorist-related mass casualty (MasCal) situations, the Terror and Disaster Surgical Care (TDSC®) course was developed and imparts special medical and surgical knowledge as well as a scenario-based training in surgical decision-making. The TDSC® course focusses on the scenario-related provision of surgical care and distribution of the limited resources to enable survival for as many patients as possible.To improve individualized trauma care course formats, such as the Advanced Trauma Life Support (ATLS®) were established and are nowadays widespread in Germany. It could be shown that standardized approaches and algorithm-based treatment could improve the outcome of trauma victims. Faced with the present day permanent risk of a possible terrorist-related MasCal situation, the question arises how and to what extent elements and principles of both course formats (TDSC® and ATLS®) could be used to improve and organize the initial care in a terrorist-linked MasCal incident.For the first time it is shown that the key elements of both courses (primary survey of the ATLS® and the TDSC® principles: categorization, prioritization, disposition and realization) could be established and integratively used to structure the initial intrahospital medical and surgical care.

LEGUME-MAIZE ROTATION OR RELAY? OPTIONS FOR ECOLOGICAL INTENSIFICATION OF SMALLHOLDER FARMS IN THE GUINEA SAVANNA OF NORTHERN GHANA.

Soil nutrient constraints coupled with erratic rainfall have led to poor crop yields and occasionally to crop failure in sole cropping in the Guinea savanna of West Africa. We explored different maize-grain legume diversification and intensification options that can contribute to mitigating risks of crop failure, increase crop productivity under different soil fertility levels, while improving soil fertility due to biological N2-fixation by the legume. There were four relay patterns with cowpea sown first and maize sown at least 2 weeks after sowing (WAS) cowpea; two relay patterns with maize sown first and cowpea sown at least 3 WAS maize in different spatial arrangements. These were compared with groundnut-maize, soybean-maize, fallow-maize and continuous maize rotations in fields high, medium and poor in fertility at a site each in the southern (SGS) and northern (NGS) Guinea savanna of northern Ghana. Legumes grown in the poorly fertile fields relied more on N2-fixation for growth leading to generally larger net N inputs to the soil. Crop yields declined with decreasing soil fertility and were larger in the SGS than in the NGS due to more favourable rainfall and soil fertility. Spatial arrangements of relay intercrops did not have any significant impact on maize and legume grain yields. Sowing maize first followed by a cowpea relay resulted in 0.18-0.26 t ha-1 reduction in cowpea grain yield relative to cowpea sown from the onset. Relaying maize into cowpea led to a 0.29-0.64 t ha-1 reduction in maize grain yield relative to maize sown from the onset in the SGS. In the NGS, a decline of 0.66 and 0.82 t ha-1 in maize grain yield relative to maize sown from the onset was observed due to less rainfall received by the relay maize. Groundnut and soybean induced 0.38-1.01 t ha-1 more grain yield of a subsequent maize relative to continuous maize, and 1.17-1.71 t ha-1 more yield relative to relay maize across both sites. Accumulated crop yields over both years suggest that sowing maize first followed by cowpea relay is a promising ecological intensification option besides the more common legume-maize rotation in the Guinea savanna, as it was comparable with soybean-maize rotation and more productive than the other treatments.

Guidelines for conducting epidemiological studies of blast injury.

Blast injuries are often caused by more than one mechanism, do not occur in isolation, and typically elicit a secondary multi-system response. Research efforts often do not separate blast injuries caused by blast waves from those caused by blunt force trauma and other mechanisms. 15 experts from nine different NATO nations developed in the HFM Research Task Group (RTG; HFM-234 (RTG)) 'Environmental Toxicology of Blast Exposures: Injury Metrics, Modelling, Methods and Standards' Guidelines for Conducting Epidemiological Studies of Blast Injury. This paper describes these guidelines, which are intended to provide blast injury researchers and clinicians with a basic set of recommendations for blast injury epidemiological study design and data collection that need to be considered and described when conducting prospective longitudinal studies of blast injury.

Guidelines for using animal models in blast injury research.

Blast injury is a very complex phenomenon and frequently results in multiple injuries. One method to investigate the consequences of blast injuries is with the use of living systems (animal models). The use of animals allows the examination and evaluation of injury mechanisms in a more controlled manner, allowing variables such as primary or secondary blast injury for example, to be isolated and manipulated as required. To ensure a degree of standardisation across the blast research community a set of guidelines which helps researchers navigate challenges of modelling blast injuries in animals is required. This paper describes the guidelines for Using Animal Models in Blast Injury Research developed by the NATO Health Factors and Medicine (HFM) Research Task Group 234.

Low copy numbers of complement C4 and homozygous deficiency of C4A may predispose to severe disease and earlier disease onset in patients with systemic lupus erythematosus.

Objectives Low copy numbers and deletion of complement C4 genes are potent risk factors for systemic lupus erythematosus (SLE). However, it is not known whether this genetic association affects the clinical outcome. We investigated C4 copy number variation and its relationship to clinical and serological features in a Northern European lupus cohort. Methods We genotyped the C4 gene locus using polymerase chain reaction (PCR)-based TaqMan assays in 169 patients with SLE classified according to the 1997 revised American College of Rheumatology (ACR) criteria and in 520 matched controls. In the patient group the mean C4 serum protein concentrations nephelometrically measured during a 12-month period prior to genetic analysis were compared to C4 gene copy numbers. Severity of disease was classified according to the intensity of the immunosuppressive regimens applied and compared to C4 gene copy numbers, too. In addition, we performed a TaqMan based analysis of three lupus-associated single-nucleotide polymorphisms (SNPs) located inside the major histocompatibility complex (MHC) to investigate the independence of complement C4 in association with SLE. Results Homozygous deficiency of the C4A isotype was identified as the strongest risk factor for SLE (odds ratio (OR) = 5.329; p = 7.7 × 10-3) in the case-control comparison. Moreover, two copies of total C4 were associated with SLE (OR = 3.699; p = 6.8 × 10-3). C4 serum levels were strongly related to C4 gene copy numbers in patients, the mean concentration ranging from 0.110 g/l (two copies) to 0.256 g/l (five to six copies; p = 4.9 × 10-6). Two copies of total C4 and homozygous deletion of C4A were associated with a disease course requiring cyclophosphamide therapy (OR = 4.044; p = 0.040 and OR = 5.798; p = 0.034, respectively). Homozygous deletion of C4A was associated with earlier onset of SLE (median 24 vs. 34 years; p = 0.019) but not significant after correction for multiple testing. SNP analysis revealed a significant association of HLA-DRB1*0301 with SLE (OR = 2.231; p = 1.33 × 10-5). Conclusions Our findings confirm the important role of complement C4 genes in the development of SLE. Beyond the impact on the susceptibility for lupus, C4 copy numbers may be related to earlier onset and a more severe course of the disease. The association of homozygous deletion of C4A and SLE is accompanied by the presence of HLA-DRB1*0301 without a proven pathophysiological mechanism.

Small dense LDL cholesterol in human subjects with different chronic inflammatory diseases.

BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.

Understanding variability in the benefits of N2-fixation in soybean-maize rotations on smallholder farmers' fields in Malawi.

Soybean production can contribute to the nitrogen economy of smallholder farming systems, but our understanding of factors explaining variability in nitrogen fixation and rotational benefits across farms and regions is limited. Biological nitrogen fixation (BNF) was quantified with the natural abundance method in 150 farmer-managed soybean plots under different varieties and inputs in Dowa, Mchinji and Salima districts of Malawi. Soybean yielded on average 1.2 t ha-1 grain and the above-ground biomass at mid pod filling (R5.5) was 2.8 t ha-1 and contained in total 63 kg ha-1 nitrogen derived from the atmosphere (Ndfa). Locally sourced varieties obtained a larger %Ndfa (65%) than the 'improved' variety Nasoko (53%). The %Ndfa was positively associated with soil sand content, sowing date, plant population and biomass accumulation, but it was not affected by inoculation with rhizobia or the combination of inoculation and NPK fertiliser application. Quantities of N2 fixed differed between regions and years, and was enhanced by applying inoculant and fertiliser together, leading to more biomass accumulation and larger grain yields. Soil available P and exchangeable K contents also increased the total amount of N2 fixed. In a related trial, continuous maize yields were compared with maize following soybean in 53 farmer-managed fields. Average yield in continuous maize was 2.5 t ha-1, while maize after soybean produced 3.5 t ha-1 (139% of continuous maize). Farmers with higher maize yields, who applied external nutrient inputs, and with a larger value of household assets achieved greater yield responses to rotation with soybean. A relative yield increase of more than 10% was observed on 59, 90 and 77% of the fields in Dowa, Mchinji and Salima respectively. We conclude that fields of soybean and maize that receive adequate nutrient inputs and good management to ensure good yields benefit most in terms of quantities of N2 fixed by the legume and the yield response of the following maize crop. The results suggest that the promotion of soybean-maize rotations should be done through an integrated approach including the promotion of appropriate soil and crop management techniques. Furthermore, they suggest that wealthier households are more likely to apply adequate nutrient inputs and good crop management practices and are likely to receive larger maize yield responses to the incorporation of soybean.

Sustainable intensification through rotations with grain legumes in Sub-Saharan Africa: A review.

We conducted a systematic review of literature on the residual effects of grain legumes in cereal-based systems of sub-Saharan Africa (SSA) to quantify the magnitude and variability of rotational effects, to explore the importance of environmental and management factors in determining variability and to evaluate the evidence of the different mechanisms that explain rotational effects. We retrieved 44 unique publications providing 199 observations comparing continuous cereal performance with that of a grain legume-cereal rotation. The overall mean yield increase of 0.49 t grain ha-1, equal to an increase of 41% of the continuous cereal yield, is highly significant, but the variability in residual effects is large. Effects were more pronounced in southern Africa, the highlands of East Africa and the Guinea savannah, and less in the humid forest/derived savannah of West Africa and the Sudano-Sahelian zone. Maize showed stronger yield responses after a legume than millet and sorghum. Agro-ecological zone and cereal type were however confounded. All grain legume types significantly improved cereal yields, with stronger residual effects observed after soybean and groundnut than after cowpea. Fertiliser N application to cereals reduces the residual effects of legumes, but the response at 60-120 kg N ha-1 still equalled 0.32 t ha-1 or 59% of the response when no N is applied. The sustained benefits with large N applications indicate the importance of non-N effects. While mechanisms for improved soil P availability after grain legumes have been studied in some detail, it remains uncertain how important these are in farmers' fields. Grain legumes are unlikely to have a major influence on the availability of nutrients other than N and P, or on soil pH. Beneficial impacts of grain legumes on soil organic matter content can occur if legumes contribute to a greater overall cropping productivity, but studies generally report no such impacts. Evidence of impacts of grain legumes on weeds is limited to striga. Studies on the impacts on nematode pressure in cereals are inconclusive, probably because legumes act as a host for some of the key nematode genera that harm maize. The impact on the pressure of other pests and diseases in cereals is probably important, but evidence on this from SSA is lacking. Future research on N2-fixation by grain legumes and residual N benefits should focus on explaining the wide variability observed among sites. There is a clear need for more detailed mechanistic studies to assess the occurrence and relevance of non-N effects of grain legumes, particularly in relation to common pests and diseases in cereals.

N2-fixation and N contribution by grain legumes under different soil fertility status and cropping systems in the Guinea savanna of northern Ghana.

Continuous cereal-based cropping has led to a rapid decline in soil fertility in the Guinea savanna agro-ecological zone of northern Ghana with corresponding low crop yields. We evaluated the effects of cropping system and soil fertility status on grain yields and N2-fixation by grain legumes and net N contribution to soil fertility improvement in contrasting sites in this agro-ecological zone. Maize was intercropped with cowpea, soybean and groundnut within a row, with a maize stand alternated with two equally spaced cowpea or groundnut stands and in the maize-soybean system, four equally spaced soybean stands. These intercrops were compared with sole crops of maize, cowpea, soybean and groundnut in fertile and poorly fertile fields at sites in the southern (SGS) and the northern (NGS) Guinea savanna. The proportion of N derived from N2-fixation (%Ndfa) was comparable between intercrops and sole crops. However, the amount of N2-fixed was significantly larger in sole crops due to a greater biomass accumulation. Legumes in poorly fertile fields had significantly smaller shoot δ15N enrichment (-2.8 to +0.7‰) and a larger %Ndfa (55-94%) than those in fertile fields (-0.8 to +2.2‰; 23-85%). The N2-fixed however was larger in fertile fields (16-145 kg N ha-1) than in poorly fertile fields (15-123 kg N ha-1) due to greater shoot dry matter and N yields. The legumes grown in the NGS obtained more of their N requirements from atmospheric N2-fixation (73-88%) than legumes grown in the SGS (41-69%). The partial soil N balance (in kg ha-1) was comparable between intercrops (-14 to 21) and sole legumes (-8 to 23) but smaller than that of sole maize receiving N fertiliser (+7 to +34). With other N inputs (aerial deposition) and outputs (leaching and gaseous losses) unaccounted for, there is uncertainty surrounding the actual amount of soil N balances of the cropping systems, indicating that partial N balances are not reliable indicators of the sustainability of cropping systems. Nevertheless, the systems with legumes seem more attractive due to several non-N benefits. Our results suggest that soybean could be targeted in the SGS and cowpea in the NGS for greater productivity while groundnut is suited to both environments. Grain legumes grown in poorly fertile fields contributed more net N to the soil but growing legumes in fertile fields seems more lucrative due to greater grain and stover yields and non-N benefits.

[Update on gunshot wounds to extremities]. / Update zu Schussverletzungen der Extremitäten.

Due to recent rampage and terror attacks in Europe, gunshot wounds have become a focus of attention even though they are still rare in Europe. Approximately 50% of gunshot wounds affect the extremities and to understand the sequelae, a basic knowledge of wound ballistics is indispensable. The energy transmitted from the bullet to the tissue is responsible for the severity of the injury and is dependent on the type of weapon and ammunition. A differentiation is made between low-energy injuries caused, e.g. by pistols and high-energy injuries mostly caused by rifles. The higher energy transfer to the tissue in high-energy injuries, results in a temporary wound cavity in addition to the permanent wound channel with extensive soft tissue damage. High-energy gunshot fractures are also more extensive compared to those of low energy injuries. Debridement seems to be necessary for almost all gunshot wounds. Fractures should be temporarily stabilized with an external fixator due to contamination.

Single Nucleotide Polymorphisms and Long-Term Clinical Outcome in Renal Transplant Patients: A Validation Study.

Genome-wide association studies (GWAS) are designed to investigate single nucleotide polymorphisms (SNPs) and the association with a clinical phenotype. A previous GWAS performed in 300 renal transplant recipients identified two SNPs (rs3811321 and rs6565887) associated with serum creatinine and clinical outcome. We sought to validate these findings. Genotyping of the two SNPs was performed using Taqman assays in 1638 Caucasians participating in the Assessment of LEscol in Renal Transplant (ALERT) study. Primary endpoint was death-censored graft loss, and secondary endpoint was all-cause mortality. Applying Cox regression, no crude association to graft loss was found for rs3811321 on chromosome 14 (hazard ratio [HR] 0.87, 95% CI 0.59-1.29, p = 0.50) or rs6565887 on chromosome 18 (HR 0.88, CI 0.62-1.25, p = 0.48). Multivariable adjustments did not change results, nor did evaluation of the number of risk alleles formed by the two SNPs. No association with mortality was detected. In conclusion, an impact of two SNPs on chromosomes 14 and 18 on death-censored graft survival or all-cause mortality was not confirmed. Our results emphasize the importance of validating findings from high-throughput genetics studies and call for large collaborative research initiatives in the field of transplantation outcomes.

BASALIT trial: double-blind placebo-controlled allergen immunotherapy with rBet v 1-FV in birch-related soya allergy.

BACKGROUND: Conflicting results exist on the effect of allergen immunotherapy (AIT) on pollen-related food allergy. We aimed to investigate the efficacy of one-year AIT with the folding variant (FV) of recombinant (r) Bet v 1 on birch-related soya allergy. METHODS: Of 138 subjects with Bet v 1 sensitization, 82 were positive at double-blind placebo-controlled food challenge (DBPCFC) with soya. A total of 56 of 82 were randomized in the ratio of 2:1 (active: placebo). Per-protocol population (PPP) had received ≥150 µg of allergen or placebo preparation. OUTCOME MEASURES: lowest observed adverse effect levels (LOAEL), postinterventional occurrence of objective signs (objS) at any dose level, sIgE/IgG4 against Bet v 1 and Gly m 4. Between-group changes were investigated (ancova, Mann-Whitney U-test, Fisher exact test). RESULTS: Baseline characteristics including LOAELs were comparable in both groups with objS and subjS occurring in 82% and 95% of active (n = 38) vs 78% and 83% of placebo group (n = 18). After AIT, objS occurred in 24% and 47%, respectively. LOAEL group differences showed a beneficial tendency (P = 0.081) for LOAELobjective in PPP (30 active, 15 placebo). sIgG4 raised only in active group (Bet v 1: P = 0.054, Gly m 4: P = 0.037), and no relevant changes occurred for sIgE. Only 56% of the intended sample size was recruited. CONCLUSION: For the first time, we present data on the effect of rBet v 1-FV on birch-related soya allergy. rBet v 1-FV AIT induced significant immunogenic effects. Clinical assessment showed a tendency in favour of the active group but did not reach statistical significance.