Bovine IgG Prevents Experimental Infection With RSV and Facilitates Human T Cell Responses to RSV.

Respiratory syncytial virus (RSV) infections represent a major burden of disease in infants and are the second most prevalent cause of death worldwide. Human milk immunoglobulins provide protection against RSV. However, many infants depend on processed bovine milk-based nutrition, which lacks intact immunoglobulins. We investigated the potential of bovine antibodies to neutralize human RSV and facilitate-cell immune activation. We show cow's milk IgG (bIgG) and Intravenous Immunoglobulin (IVIG) have a similar RSV neutralization capacity, even though bIgG has a lower pre-F to post-F binding ratio compared to human IVIG, with the majority of bIgG binding to pre-F. RSV is better neutralized with human IVIG. Consequently, we enriched RSV specific T cells by culturing human PBMC with a mixture of RSV peptides, and used these T cells to study the effect of bIgG and IVIG on the activation of pre-F-pecific T cells. bIgG facilitated in vitro T cell activation in a similar manner as IVIG. Moreover, bIgG was able to mediate T cell activation and internalization of pathogens, which are prerequisites for inducing an adaptive viral response. Using in vivo mouse experiments, we showed that bIgG is able to bind the murine activating IgG Fc Receptors (FcγR), but not the inhibiting FcγRII. Intranasal administration of the monoclonal antibody palivizumab, but also of bIgG and IVIG prevented RSV infection in mice. The concentration of bIgG needed to prevent infection was ~5-fold higher compared to IVIG. In conclusion, the data presented here indicate that functionally active bIgG facilitates adaptive antiviral T cell responses and prevents RSV infection in vitro and in vivo.

Microsieving in primary treatment: effect of chemical dosing.

Primary and chemically enhanced primary wastewater treatment with microsieving (disc or drum filtration) was studied at the large pilot scale at seven municipal wastewater treatment plants in Europe. Without chemical dosing, the reduction of suspended solids (SS) was (on average) 50% (20-65%). By introducing chemically enhanced primary treatment and dosing with cationic polymer only, SS removal could be controlled and increased to >80%. A maximum SS removal of >90% was achieved with a chemical dosing of >0.007 mg polymer/mg influent SS and 20 mg Al(3+)/L or 30 mg Fe(3+)/L. When comparing sieve pore sizes of 30-40 µm with 100 µm, the effluent SS was comparable, indicating that the larger sieve pore size could be used due to the higher loading capacity for the solids. Phosphorus removal was adjusted with the coagulant dose, and a removal of 95-97% was achieved. Moreover, microsieving offers favourable conditions for automated dosing control due to the low retention time in the filter.

Multicentre randomized controlled trial comparing ferric(III)carboxymaltose infusion with oral iron supplementation in the treatment of preoperative anaemia in colorectal cancer patients.

BACKGROUND: At least a third of patients with a colorectal carcinoma who are candidate for surgery, are anaemic preoperatively. Preoperative anaemia is associated with increased morbidity and mortality. In general practice, little attention is paid to these anaemic patients. Some will have oral iron prescribed others not. The waiting period prior to elective colorectal surgery could be used to optimize a patients' physiological status. The aim of this study is to determine the efficacy of preoperative intravenous iron supplementation in comparison with the standard preoperative oral supplementation in anaemic patients with colorectal cancer. METHODS/DESIGN: In this multicentre randomized controlled trial, patients with an M0-staged colorectal carcinoma who are scheduled for curative resection and with a proven iron deficiency anaemia are eligible for inclusion. Main exclusion criteria are palliative surgery, metastatic disease, neoadjuvant chemoradiotherapy (5 × 5 Gy = no exclusion) and the use of Recombinant Human Erythropoietin within three months before inclusion or a blood transfusion within a month before inclusion. Primary endpoint is the percentage of patients that achieve normalisation of the haemoglobin level between the start of the treatment and the day of admission for surgery. This study is a superiority trial, hypothesizing a greater proportion of patients achieving the primary endpoint in favour of iron infusion compared to oral supplementation. A total of 198 patients will be randomized to either ferric(III)carboxymaltose infusion in the intervention arm or ferrofumarate in the control arm. This study will be performed in ten centres nationwide and one centre in Ireland. DISCUSSION: This is the first randomized controlled trial to determine the efficacy of preoperative iron supplementation in exclusively anaemic patients with a colorectal carcinoma. Our trial hypotheses a more profound haemoglobin increase with intravenous iron which may contribute to a superior optimisation of the patient's condition and possibly a decrease in postoperative morbidity. TRIAL REGISTRATION: ClincalTrials.gov: NCT02243735 .

Gastrointestinal symptoms in low-dose aspirin users: a comparison between plain and buffered aspirin.

BACKGROUND: Aspirin is associated with gastrointestinal side effects such as gastric ulcers, gastric bleeding and dyspepsia. High-dose effervescent calcium carbasalate (ECC), a buffered formulation of aspirin, is associated with reduced gastric toxicity compared with plain aspirin in healthy volunteers, but at lower cardiovascular doses no beneficial effects were observed. AIM: To compare the prevalence of self-reported gastrointestinal symptoms between low-dose plain aspirin and ECC. METHODS: A total of 51,869 questionnaires were sent to a representative sample of the Dutch adult general population in December 2008. Questions about demographics, gastrointestinal symptoms in general and specific symptoms, comorbidity, and medication use including bioequivalent doses of ECC (100 mg) and plain aspirin (80 mg) were stated. We investigated the prevalence of self-reported gastrointestinal symptoms on ECC compared with plain aspirin using univariate and multivariate logistic regression analyses. RESULTS: A total of 16,715 questionnaires (32 %) were returned and eligible for analysis. Of these, 911 (5 %) respondents reported the use of plain aspirin, 633 (4 %) ECC and 15,171 reported using neither form of aspirin (91 %). The prevalence of self-reported gastrointestinal symptoms in general was higher in respondents using ECC (27.5 %) compared with plain aspirin (26.3 %), but did not differ significantly with either univariate (OR 1.06, 95 %CI 0.84-1.33), or multivariate analysis (aOR 1.08, 95 %CI 0.83-1.41). Also, none of the specific types of symptoms differed between the two aspirin formulations. CONCLUSIONS: In this large cohort representative of the general Dutch population, low-dose ECC is not associated with a reduction in self-reported gastrointestinal symptoms compared with plain aspirin.

Incorporation of bioactive glass in calcium phosphate cement: An evaluation.

Bioactive glasses (BGs) are known for their unique ability to bond to living bone. Consequently, the incorporation of BGs into calcium phosphate cement (CPC) was hypothesized to be a feasible approach to improve the biological performance of CPC. Previously, it has been demonstrated that BGs can successfully be introduced into CPC, with or without poly(d,l-lactic-co-glycolic) acid (PLGA) microparticles. Although an in vitro physicochemical study on the introduction of BG into CPC was encouraging, the biocompatibility and in vivo bone response to these formulations are still unknown. Therefore, the present study aimed to evaluate the in vivo performance of BG supplemented CPC, either pure or supplemented with PLGA microparticles, via both ectopic and orthotopic implantation models in rats. Pre-set scaffolds in four different formulations (1: CPC; 2: CPC/BG; 3: CPC/PLGA; and 4: CPC/PLGA/BG) were implanted subcutaneously and into femoral condyle defects of rats for 2 and 6 weeks. Upon ectopic implantation, incorporation of BG into CPC improved the soft tissue response by improving capsule and interface quality. Additionally, the incorporation of BG into CPC and CPC/PLGA showed 1.8- and 4.7-fold higher degradation and 2.2- and 1.3-fold higher bone formation in a femoral condyle defect in rats compared to pure CPC and CPC/PLGA, respectively. Consequently, these results highlight the potential of BG to be used as an additive to CPC to improve the biological performance for bone regeneration applications. Nevertheless, further confirmation is necessary regarding long-term in vivo studies, which also have to be performed under compromised wound-healing conditions.

Doses and risks from uranium are not increased significantly by interactions with natural background photon radiation.

The impact of depleted uranium (DU) on human health has been the subject of much conjecture. Both the chemical and radiological aspects of its behaviour in the human body have previously been investigated in detail, with the radiological impact being assumed to be linked to the alpha decay of uranium. More recently, it has been proposed that the accumulation in tissue of high-Z materials, such as DU, may give rise to enhanced local energy deposition in the presence of natural background photon radiation due to the high photoelectric interaction cross sections of high-Z atoms. It is speculated that, in addition to producing short-range photoelectrons, these events will be followed by intense Auger and Coster-Kronig electron emission, thereby causing levels of cell damage that are unaccounted for in conventional models of radiological risk. In this study, the physical and biological bases of these claims are investigated. The potential magnitudes of any effect are evaluated and discussed, and compared with the risks from other radiological or chemical hazards. Monte Carlo calculations are performed to estimate likely energy depositions due to the presence of uranium in human tissues in photon fields: whole body doses, organ doses in anthropomorphic phantoms and nano-/micro-dosimetric scenarios are each considered. The proposal is shown generally to be based on sound physics, but overall the impact on human health is expected to be negligible.

Determination of genetic structure of germplasm collections: are traditional hierarchical clustering methods appropriate for molecular marker data?

Despite the availability of newer approaches, traditional hierarchical clustering remains very popular in genetic diversity studies in plants. However, little is known about its suitability for molecular marker data. We studied the performance of traditional hierarchical clustering techniques using real and simulated molecular marker data. Our study also compared the performance of traditional hierarchical clustering with model-based clustering (STRUCTURE). We showed that the cophenetic correlation coefficient is directly related to subgroup differentiation and can thus be used as an indicator of the presence of genetically distinct subgroups in germplasm collections. Whereas UPGMA performed well in preserving distances between accessions, Ward excelled in recovering groups. Our results also showed a close similarity between clusters obtained by Ward and by STRUCTURE. Traditional cluster analysis can provide an easy and effective way of determining structure in germplasm collections using molecular marker data, and, the output can be used for sampling core collections or for association studies.

A life cycle approach to the management of household food waste - A Swedish full-scale case study.

Environmental impacts from incineration, decentralised composting and centralised anaerobic digestion of solid organic household waste are compared using the EASEWASTE LCA-tool. The comparison is based on a full scale case study in southern Sweden and used input-data related to aspects such as source-separation behaviour, transport distances, etc. are site-specific. Results show that biological treatment methods - both anaerobic and aerobic, result in net avoidance of GHG-emissions, but give a larger contribution both to nutrient enrichment and acidification when compared to incineration. Results are to a high degree dependent on energy substitution and emissions during biological processes. It was seen that if it is assumed that produced biogas substitute electricity based on Danish coal power, this is preferable before use of biogas as car fuel. Use of biogas for Danish electricity substitution was also determined to be more beneficial compared to incineration of organic household waste. This is a result mainly of the use of plastic bags in the incineration alternative (compared to paper bags in the anaerobic) and the use of biofertiliser (digestate) from anaerobic treatment as substitution of chemical fertilisers used in an incineration alternative. Net impact related to GWP from the management chain varies from a contribution of 2.6kg CO(2)-eq/household and year if incineration is utilised, to an avoidance of 5.6kg CO(2)-eq/household and year if choosing anaerobic digestion and using produced biogas as car fuel. Impacts are often dependent on processes allocated far from the control of local decision-makers, indicating the importance of a holistic approach and extended collaboration between agents in the waste management chain.

Manual or exercise therapy for long-standing adductor-related groin pain: a randomised controlled clinical trial.

HYPOTHESIS: A multi-modal treatment program (MMT) is more effective than exercise therapy (ET) for the treatment of long-standing adductor-related groin pain. STUDY DESIGN: Single blinded, prospective, randomised controlled trial. PATIENTS: Athletes with pain at the proximal insertion of the adductor muscles on palpation and resisted adduction for at least two months. INTERVENTIONS: ET: a home-based ET and a structured return to running program with instruction on three occasions from a sports physical therapist. MMT: Heat, Van den Akker manual therapy followed by stretching and a return to running program. PRIMARY OUTCOME: time to return to full sports participation. SECONDARY OUTCOME MEASURES: objective outcome score and the visual analogue pain score during sports activities. Outcome was assessed at 0, 6, 16 and 24 weeks. RESULTS: Athletes who received MMT returned to sports quicker (12.8 weeks, SD 6.0) than athletes in the ET group (17.3 weeks, SD 4.4. p = 0.043). Only 50-55% of athletes in both groups made a full return to sports. There was no difference between the groups in objective outcome (p = 0.72) or VAS during sports (p = 0.12). CONCLUSIONS: The multi-modal program resulted in a significantly quicker return to sports than ET plus return to running but neither treatment was very effective.

A Monte Carlo analysis of possible cell dose enhancement effects by uranium microparticles in photon fields.

Uranium microparticles (radii: 50 nm-1.25 µm) were modelled surrounded by tissue and exposed to natural background radiation, in order to investigate potential dose enhancements from photon interactions. Generally, the results depended on the microparticle size. For a 0.5 µm radius microparticle in an isotropic field, it was found that the combined photon/electron doses deposited in 1 and 10 µm radii shells around it were raised by factors of ∼3.8 and ∼1.1, respectively; for a typical background photon fluence rate, these would correspond to increased energy depositions of a few 10s and a few 100s of eV y(-1), which are far less than the likely deposition rate resulting from the radioactive decay of a (238)U microparticle. The health hazard from uranium microparticle interactions with background photons was concluded to be negligible.

Semi-standardised homeopathic treatment of premenstrual syndrome with a limited number of medicines: feasibility study.

BACKGROUND: Individualised homeopathy involves a large number of possible medicines. For clinical research purposes it is desirable to limit this number, create more consistency between prescribers and optimising the accuracy of prescription. Using a semi-standardised treatment protocol, we aimed to improve homeopathic management of targeted subgroups of women with premenstrual syndrome/symptoms (PMS/S). OBJECTIVES: To design a semi-standardised protocol for individualised prescribing in PMS/S with a limited number of homeopathic medicines, and to explore the feasibility of working with it in daily homeopathic practice. METHODS: With help of an expert panel, homeopathic medicines were selected, as well as predictive symptoms and characteristics (keynotes) for each medicine. With those, we designed a patient questionnaire and a diagnostic algorithm. The patient questionnaire contained 123 questions, representing potential predictive symptoms for 11 homeopathic medicines for PMS/S. The medicines selected (in rank order) were Sep, Nat-m, Lach, Cimic, Lac-c, Puls, Calc, Lil-t, Mag-p, Mag-c, Phos. In a feasibility study 20 homeopathic doctors used the protocol in daily practice. The diagnosis was confirmed by daily rating of pre-defined symptoms during two consecutive menstrual cycles. The acceptability and feasibility of the protocol were evaluated after 3 months follow-up, at which time we also measured changes in premenstrual symptom scores and patient-reported changes in symptoms and general health. RESULTS: The doctors mostly complied with the protocol and valued the computerised diagnostic algorithm as a useful tool for homeopathic medicine selection. 33 patients completed 3 months follow-up. By then, 19 patients still taking the first medicine on the basis of the algorithm. We received valid symptom records of 30 patients. Premenstrual symptom scores dropped by 50% or more in 12 patients and by 30-50% in 6 patients; scores dropped by less than 30% or increased in 12 patients. Recruitment of patients (n=38 in 9 months) proved difficult. Adherence to the diaries and the questionnaire was satisfactory. CONCLUSIONS: It is feasible to use a semi-standardised protocol for individualised homeopathic prescribing in PMS, in daily practice. Its predictive value and the percentage of women with PMS/S helped by the selected medicines remain to be evaluated in further research. In future research, active promotion will be needed to recruit patients.

DC-SCRIPT: nuclear receptor modulation and prognostic significance in primary breast cancer.

BACKGROUND: Nuclear receptors, including estrogen receptor (ER), progesterone receptor (PR)-B, peroxisome proliferator-activated receptor gamma, and retinoic acid receptor alpha, have been implicated in breast cancer etiology and progression. We investigated the role of dendritic cell-specific transcript (DC-SCRIPT) as coregulator of these nuclear receptors and as a prognostic factor in breast cancer. METHODS: The effect of DC-SCRIPT on the transcriptional activity of nuclear receptors was assessed by luciferase reporter assays. DC-SCRIPT expression in normal and tumor tissue from breast cancer patients was analyzed by polymerase chain reaction and immunohistochemistry. The prognostic value of tumor DC-SCRIPT mRNA expression was assessed in three independent cohorts of breast cancer patients: a discovery group (n = 47) and a validation group (n = 97) (neither of which had received systemic adjuvant therapy) and in a tamoxifen-treated validation group (n = 68) by using a DC-SCRIPT to porphobilinogen deaminase transcript ratio cutoff of 0.15 determined in the discovery group. Univariate and multivariable Cox proportional hazards model analyses were performed. All statistical tests were two-sided. RESULTS: DC-SCRIPT suppressed ER- and PR-mediated transcription in a ligand-dependent fashion, whereas it enhanced the retinoic acid receptor alpha- and peroxisome proliferator-activated receptor gamma-mediated transcription. In breast tissue samples from nine patients, DC-SCRIPT mRNA was expressed at lower levels in the tumor than in the corresponding normal tissue (P = .010). Patients in the discovery group with high tumor DC-SCRIPT mRNA levels (66%) had a longer disease-free interval than those with a low DC-SCRIPT mRNA level (34%) (hazard ratio [HR] of recurrence for high vs low DC-SCRIPT level = 0.23, 95% confidence interval [CI] = 0.06 to 0.93, P = .039), which was confirmed in the validation group (HR of recurrence = 0.50, 95% CI = 0.26 to 0.95, P = .034). This prognostic value was confined to patients with ER- and/or PR-positive tumors (discovery group: HR of recurrence = 0.16, 95% CI = 0.03 to 0.89, P = .030; validation group: HR of recurrence = 0.42, 95% CI = 0.19 to 0.91, P = .028) and was also observed in the second validation group (HR = 0.46, 95% CI = 0.22 to 0.97, P = .040). DC-SCRIPT was an independent prognostic factor after correction for tumor size, lymph node status, and adjuvant therapy (n = 145; HR = 0.50, 95% CI = 0.29 to 0.85, P = .010). CONCLUSION: DC-SCRIPT is a key regulator of nuclear receptor activity that has prognostic value in breast cancer.

Treatment of longstanding groin pain in athletes: a systematic review.

The aims of this study were to determine (1) the kinds of treatments applied for longstanding groin pain (LGP) in athletes; (2) the results; and (3) the levels of evidence for the interventions. Digital databases P were searched for articles describing the effects of interventions for LGP in athletes. Treatment of LGP in athletes can consist of conservative measures such as rest or restricted activity, active or passive physical therapy, steroid injections or dextrose prolotherapy. Studies describing surgery generally mention failure of conservative measures, although a description of these conservative measures is mostly lacking. During surgery, a reinforcement of the abdominal wall is applied in most cases, using an open or laparoscopic approach. There is level I evidence that physical therapy aiming at strengthening and coordinating the muscles stabilizing hip and pelvis has superior results compared with passive physical therapy. For patients with a positive herniography and/or positive ilioinguinal or iliohypogastric nerve block tests, there are indications (level II) that surgery results in earlier return to sport compared with exercise therapy. Possibly, laparoscopic intervention might result in an earlier return to sport compared with open approach surgery (level III). For different clinical diagnoses, the same or similar surgical interventions were performed.

Introduction of gelatin microspheres into an injectable calcium phosphate cement.

For tissue engineered bone constructs, calcium phosphate cement (CPC) has a high potential as scaffold material because of its biocompatibility and osteoconductivity. However, in vivo resorption and tissue ingrowth is slow. To address these issues, microspheres can be incorporated into the cement, which will create macroporosity after in situ degradation. The goal of this study was to investigate the handling properties and degradation characteristics of CPC containing gelatin microspheres. Setting time and injectability were determined and an in vitro degradation study was performed. Samples were assayed on mass, compression strength, E-modulus, and morphology. A supplementary degradation test with gelatin microspheres was performed to investigate the influence of physical conditions inside the cement on microsphere stability. The gelatin microsphere CPCs were easy to inject and showed initial setting times of less than 3 min. After 12-weeks in vitro degradation no increase in macroporosity was observed, which was supported by the small mass loss and stabilizing mechanical strength. Even a clear densification of the composite was observed. Explanations for the lack of macroporosity were recrystallization of the cement onto or inside the gelatin spheres and a delayed degradation of gelatin microspheres inside the scaffold. The supplementary degradation test showed that the pH is a factor in the delayed gelatin microsphere degradation. Also differences in degradation rate between types of gelatin were observed. Overall, the introduction of gelatin microspheres into CPC renders composites with good handling properties, though the degradation characteristics should be further investigated to generate a macroporous scaffold.

The effect of combined application of TGFbeta-1, BMP-2, and COLLOSS E on the development of bone marrow derived osteoblast-like cells in vitro.

This study investigated the combined application of Transforming Growth Factor beta-1 (TGFbeta-1) and Bone Morphogenetic Protein-2 (BMP-2) to stimulate osteogenic expression in vitro. TGFbeta-1 and BMP-2 fulfill specific roles in the formation of new bone. COLLOSS E, a bone-derived collagen product containing a variety of naturally occurring growth factors, was also used. Growth factors were administered to osteoblast-like cells from rat bone marrow (RBM). Proliferation and differentiation were monitored up to 24 days, by measuring total DNA content, alkaline phosphatase activity, and calcium content. Genetic expression of a set of differentiation markers at day 7 was measured by Q-PCR. Adding BMP-2 alone induced high proliferation rates, compared to the growth factor supplemented groups, and it induced high differentiation rates, compared to the control group. Adding TGFbeta-1 combined with BMP-2, TGFbeta-1 alone, or COLLOSS E resulted in a significant decrease in proliferation rate, but an increase in differentiation rate, compared to the control group. Additive or synergistic effects of application of TGFbeta-1 and BMP-2 were not observed. The observed effects of COLLOSS E mainly resembled those of TGFbeta-1 application alone. It can be concluded that BMP-2 is the most suitable candidate for osteogenic stimulation of RBM cells in these settings.

Biologically mediated phosphorus precipitation in wastewater treatment with microalgae.

A lab-scale continuous microalgal culture was grown on sterile-filtered wastewater in order to clarify the phosphorus removing mechanisms in a microalgal treatment step that treats residual phosphorus from a hydroponic wastewater treatment pilot plant. The phosphorus assimilation was dependent on algal biomass production, whereas the chemical precipitation was dependent on phosphorus load, i.e. an increase in average precipitation rate with decreased hydraulic retention time was observed. The chemical precipitation was mainly a result of the increased pH, which was biologically mediated by the photosynthesising algae. The precipitate was composed of a calcium phosphate with magnesium included, magnesium hydroxide and calcite. A significant nitrogen removal was also experienced, which implies that the microalgal wastewater treatment is appropriate both for phosphorus and nitrogen removal.

Ceramic composites as matrices and scaffolds for drug delivery in tissue engineering.

Ceramic composites and scaffolds are popular implant materials in the field of dentistry, orthopedics and plastic surgery. For bone tissue engineering especially CaP-ceramics or cements and bioactive glass are suitable implant materials due to their osteoconductive properties. In this review the applicability of these ceramics but also of ceramic/polymer composites for bone tissue engineering is discussed, and in particular their use as drug delivery systems. Overall, the high density and slow biodegradability of ceramics is not beneficial for tissue engineering purposes. To address these issues, macroporosity can be introduced often in combination with osteoinductive growth factors and cells. Ceramics are good carriers for drugs, in which release patterns are strongly dependent on the chemical consistency of the ceramic, type of drug and drug loading. Biodegradable polymers like polylactic acid, gelatin or chitosan are used as matrices for ceramic particles or as adjuvant to calcium phosphate cements. The use of these polymers can introduce a tailored biodegradation/drug release to the ceramic material.

A systematic review of the quality of homeopathic pathogenetic trials published from 1945 to 1995.

BACKGROUND: The quality of information gathered from homeopathic pathogenetic trials (HPTs), also known as 'provings', is fundamental to homeopathy. We systematically reviewed HPTs published in six languages (English, German, Spanish, French, Portuguese and Dutch) from 1945 to 1995, to assess their quality in terms of the validity of the information they provide. METHODS: The literature was comprehensively searched, only published reports of HPTs were included. Information was extracted by two reviewers per trial using a form with 87 items. Information on: medicines, volunteers, ethical aspects, blinding, randomization, use of placebo, adverse effects, assessments, presentation of data and number of claimed findings were recorded. Methodological quality was assessed by an index including indicators of internal and external validity, personal judgement and comments of reviewers for each study. RESULTS: 156 HPTs on 143 medicines, involving 2815 volunteers, produced 20,538 pathogenetic effects (median 6.5 per volunteer). There was wide variation in methods and results. Sample size (median 15, range 1-103) and trial duration (mean 34 days) were very variable. Most studies had design flaws, particularly absence of proper randomization, blinding, placebo control and criteria for analysis of outcomes. Mean methodological score was 5.6 (range 4-16). More symptoms were reported from HPTs of poor quality than from better ones. In 56% of trials volunteers took placebo. Pathogenetic effects were claimed in 98% of publications. On average about 84% of volunteers receiving active treatment developed symptoms. The quality of reports was in general poor, and much important information was not available. CONCLUSIONS: The HPTs were generally of low methodological quality. There is a high incidence of pathogenetic effects in publications and volunteers but this could be attributable to design flaws. Homeopathic medicines, tested in HPTs, appear safe. The central question of whether homeopathic medicines in high dilutions can provoke effects in healthy volunteers has not yet been definitively answered, because of methodological weaknesses of the reports. Improvement of the method and reporting of results of HPTs are required. REFERENCES: References to all included RCTs are available on-line at.

Applicability of experience from laboratory reactors with biological phosphorus removal in full-scale plants.

Enhanced biological phosphorus removal (EBPR) has been used at many wastewater treatment plants all over the world for many years. In this study a full-scale sludge with good EBPR was tested with P-release batch tests and combined FISH/MAR (fluorescence in situ hybridisation and microautoradiography). Proposed models of PAOs and GAOs (polyphosphate- and glycogen-accumulating organisms) and microbial methods suggested from studies of laboratory reactors were found to be applicable also on sludge from full-scale plants. Dependency of pH and the uptake of both acetate and propionate were studied and used for calculations for verifying the models and results from microbial methods. All rates found from the batch tests with acetate were higher than in the batch tests with propionate, which was explained by the finding that only those parts of the bacterial community that were able to take up acetate anaerobically were able to take up propionate anaerobically.