The ethics of doing nothing. Suicide-bereavement and research: ethical and methodological considerations.

BACKGROUND: Valuable trauma-related research may be hindered when the risks of asking participants about traumatic events are not carefully weighed against the benefits of their participation in the research. METHOD: The overall aim of our population-based survey was to improve the professional care of suicide-bereaved parents by identifying aspects of care that would be amenable to change. The study population included 666 suicide-bereaved and 377 matched (2:1) non-bereaved parents. In this article we describe the parents' perceptions of their contacts with us as well as their participation in the survey. We also present our ethical-protocol for epidemiological surveys in the aftermath of a traumatic loss. RESULTS: We were able to contact 1410 of the 1423 eligible parents; eight of these parents expressed resentment towards the contact. Several participants and non-participants described their psychological suffering and received help because of the contact. A total of 666 suicide-bereaved and 377 non-bereaved parents returned the questionnaire. Just two out of the 1043 answered that they might, in the long term, be negatively affected by participation in the study; one was bereaved, the other was not. A significant minority of the parents reported being temporarily negatively affected at the end of their participation, most of them referring to feelings of sadness and painful memories. In parallel, positive experiences were widely expressed and most parents found the study valuable. CONCLUSIONS: Our findings suggest, given that the study design is ethically sound, that suicide-bereaved parents should be included in research since the benefits clearly outweigh the risks.

Full-scale sludge liquor treatment for ammonium reduction with low carbon dosage.

The separate treatment of sludge liquor, produced by dewatering anaerobic digested sludge at wastewater treatment plants, gives rise to extreme environments for nitrogen removal. A full-scale sequencing batch reactor was operated with the aim of introducing and studying denitritation as a supplement to nitritation in order to reduce operating costs. Since the main plant only has problems with ammonium reduction capacity, the initial strategy was to have sufficient ammonium reduction with optimal alkalinity production by denitrifiers, i.e. low carbon dosage and minimum alkalinity and residual oxidized ammonium in the effluent. This strategy led to an unbalanced and sensitive process because the denitrifiers were often inhibited. High dissolved oxygen (DO) readings and no decrease in oxidation-reduction potential (ORP) during anoxic phases with simultaneous ethanol dosage indicated inhibition of denitrifiers, probably by the intermediate product NO, which may have interfered with the DO sensor. Nitric oxide production was believed to be favoured in the beginning of the anoxic phase as a result of low pH and high nitrite concentration. A stable nitritation-denitritation process could be achieved when the aerobic hydraulic retention time (HRT) was decreased to the same length as the anoxic HRT, which resulted in increased unused alkalinity.

The development of the Suicidal Patient Observation Chart (SPOC): Delphi study.

Constant observation is a method used to insure the safety of suicidal inpatients. It involves structure and control as well as flexibility and the development of a relationship between the observer and the patient. It has been found that important observations may go unnoticed by the observer or fail to be communicated to the multidisciplinary team because of a lack of sufficient training and systematic documentation. We therefore conducted a Delphi survey to collect opinions on what would be important to observe during constant observation of suicidal patients. A panel of experienced clinicians, service users and researchers reached consensus on 37 of 40 observation items (92%). Of these, 28 were rated as the most important. As a result, we developed a form for systematic observer documentation in clinical practice, the Suicidal Patient Observation Chart. The Suicidal Patient Observation Chart includes the 28 items and covers 24 separate observation periods.

'A no means no'--measuring depression using a single-item question versus Hospital Anxiety and Depression Scale (HADS-D).

BACKGROUND: Depression often develops undetected; to make treatment possible, a single-item screening question may be useful. PATIENTS AND METHODS: We attempted to compare the accuracy of the single-item question 'Are you depressed?' with the seven-item Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D) among 1192 Swedish testicular cancer survivors. RESULTS: We obtained information from 974 men (82%). Fifty-nine men (6%) answered 'Yes' to the question 'Are you depressed?' while 118 (12%) answered 'I don't know' and 794 (82%) answered 'No'. Among the 794 men who answered 'No' to the question 'Are you depressed?', 790 (99.5%) were not considered as depressed according to HADS-D 11+. Of those answering 'Yes', 34% (20/59) were identified as depressed according to the same cut-off. Sensitivity of 'Yes' compared with HADS-D > or =11 was 61%, rising to 88% when 'Yes' and 'I don't know' were combined. CONCLUSION: In a population of men with a prevalence of depression similar to that of the normal population, almost none of those responding 'No' to the written question 'Are you depressed?' were depressed according to HADS-D > or =11. Adding the category 'I don't know' increases sensitivity in detecting depression.

Operation for nitritation of sludge liquor in a full-scale SBR.

At Sjölunda WWTP, a full-scale SBR for treatment of mesophilic sludge digester liquor has been operated almost a year with stable nitrite accumulation. Only nitritation of the sludge liquor is needed since the oxidized ammonium is denitrified in the first anoxic zone of the high-loaded activated sludge in the main plant. The process strategy was to have an ammonium set-point to end the aeration, a low DO concentration and a low pH set-point. An increase of pH set-point from 6.8 to 7.2 increased loss of alkalinity in the effluent and increased sodium hydroxide dosing. An increase of DO set-point from 1.1 mg O2 L(-1) to 1.3 mg O2 L(-1) markedly increased ammonia reduction rates and only slightly increased nitrate production. Today, an introduction of denitritation in the SBR will be a more cost-effective treatment of sludge liquor at Sjölunda WWTP. However, the choice of operation with only nitritation or nitritation/denitritation in sludge liquor treatment should always include a consideration of chemical costs and treatment capacity of both main plant and side-stream plant.

Utilising laboratory experiments as a first step to introduce primary sludge hydrolysis in full-scale.

Laboratory experiments have been utilised as a tool to determine the possible yield of soluble COD and VFAs from settled influent and preprecipitated sludge at Klagshamn wastewater treatment plant and to determine the degradability of the organic matter. The release of ammonium and orthophosphate from the hydrolysed sludge has been estimated. It is possible to produce soluble organic matter of good quality from settled influent and preprecipitated sludge at Klagshamn WWTP. Denitrification rates of 3.1 mg NO3-N/(g VSS x h) were found for the hydrolysate in laboratory tests. Owing to the low phosphate concentrations in the hydrolysate from preprecipitated sludge, it shows a potential for postdenitrification despite stringent phosphorus outlet demands. Calculations based on data gained from the laboratory experiments show that about 50% of the external carbon source used today can be saved with minor changes in the plant operation except that the hydrolysis has to be established. Based on these findings, full-scale experiments with internal hydrolysis in the primary clarifiers were scheduled in one of the two lines at Klagshamn WWTP for the summer of 2007.

Reducing the total discharge from a large WWTP by separate treatment of primary effluent overflow.

At many large wastewater treatment plants (WWTPs) the increased hydraulic load, caused by combined sewer systems during storm events, results in primary effluent overflow when the capacity of further treatment is exceeded. Due to stringent effluent standards, regulating the total discharge from the WWTPs, the Rya WWTP in Göteborg and the Sjölunda WWTP in Malmö will have to reduce the impact of primary effluent overflow. Separate, high rate, precipitation processes operated only during high flow conditions have been investigated in pilot units at the two WWTPs. Precipitation in existing primary settlers operated at a surface loading of 3.75 m/h removed phosphorus to 0.35 mg/l. The Actiflo process was also shown to remove suspended solids and phosphorus well. BOD was reduced by 50-60%. With such processes the overall effluent concentrations from the plants can be reduced significantly. Key upgrading features are small footprints, short start up time and high efficiency.

Upgrading the Sjölunda WWTP according to a novel process concept.

The Sjölunda wastewater treatment plant in Malmö, Sweden, was upgraded for extended nutrient removal in 1998-1999. The design was based on future effluent standards of 10 mg BOD7/l, 0.3 mg total-P/l and 8 mg total-N/l. The upgrading concept took into consideration existing processes and structures, resulting in a cost-effective and compact upgrading. To introduce nitrification, the existing trickling filters for BOD-removal were converted to a nitrifying mode. A sequencing batch reactor for nitrification of supernatant was necessary to control the ammonia load. Denitrification was accomplished in a moving bed biofilm reactor with addition of external carbon source. The future effluent standards could be met by the upgraded plant. The trickling filters were stable despite varying loading conditions. High rates and low effluent ammonia concentrations were achieved. Essential features for stable post denitrification were control strategies for carbon source dosage and avoiding phosphorus limitation.

Mortality after cerebral angiography with or without radioactive Thorotrast: an international cohort of 3,143 two-year survivors.

There are few studies on the long-term sequelae of radionuclides ingested or injected into the human body. Patients exposed to radioactive Thorotrast in the 1930s through the early 1950s provide a singular opportunity, since the administration of this radiographic contrast agent resulted in continuous exposure to alpha particles throughout life at a low dose rate. We evaluated cause-specific mortality among an international cohort of 3,143 patients injected during cerebral angiography with either Thorotrast (n = 1,736) or a similar but nonradioactive agent (n = 1,407) and who survived 2 or more years. Standardized mortality ratios (SMRs) for Thorotrast and comparison patients were calculated, and relative risks (RR), adjusted for population, age and sex, were obtained by multivariate statistical modeling. Most patients were followed until death, with only 94 (5.4%) of the Thorotrast patients known to be alive at the closure of the study. All-cause mortality (n = 1,599 deaths) was significantly elevated among Thorotrast subjects [RR 1.7; 95% confidence interval (CI) 1.5-1.8]. Significantly increased relative risks were found for several categories, including cancer (RR 2.8), benign and unspecified tumors (RR 1.5), benign blood diseases (RR 7.1), and benign liver disorders (RR 6.5). Nonsignificant increases were seen for respiratory disease (RR 1.4) and other types of digestive disease (RR 1.6). The relative risk due to all causes increased steadily after angiography to reach a threefold RR at 40 or more years (P < 0.001). Excess cancer deaths were observed for each decade after Thorotrast injection, even after 50 years (SMR 8.6; P < 0.05). Increasing cumulative dose of radiation was directly associated with death due to all causes combined, cancer, respiratory disease, benign liver disease, and other types of digestive disease. Our study confirms the relationship between Thorotrast and increased mortality due to cancer, benign liver disease, and benign hematological disease, and suggests a possible relationship with respiratory disorders and other types of digestive disease. The cumulative excess risk of cancer death remained high up to 50 years after injection with >20 ml Thorotrast and approached 50%.

M-X-I motif of semliki forest virus capsid protein affects nucleocapsid assembly.

Alphavirus budding is driven by interactions between spike and nucleocapsid proteins at the plasma membrane. The binding motif, Y-X-L, on the spike protein E2 and the corresponding hydrophobic cavity on the capsid protein were described earlier. The spike-binding cavity has also been suggested to bind an internal hydrophobic motif, M113-X-I115, of the capsid protein. In this study we found that replacement of amino acids M113 and I115 with alanines, as single or double mutations, abolished formation of intracellular nucleocapsids. The mutants could still bud efficiently, but the NCs in the released virions were not stable after removal of the membrane and spike protein layer. In addition to wild-type spherical particles, elongated multicored particles were found at the plasma membrane and released from the host cell. We conclude that the internal capsid motif has a biological function in the viral life cycle, especially in assembly of nucleocapsids. We also provide further evidence that alphaviruses may assemble and bud from the plasma membrane in the absence of preformed nucleocapsids.

A conserved leucine in the cytoplasmic domain of the Semliki Forest virus spike protein is important for budding.

Budding of alphaviruses at the plasma membrane has been shown to depend on specific amino acids of the spike protein and hydrophobic cavities of the nucleocapsid. Here the function of leucine401 in the cytoplasmic tail of the Semliki Forest virus spike protein was studied. When alanine and threonine were substituted for leucine the budding efficiency decreased. When the alanine mutant virus was passaged and sequenced a valine residue at position 401 was found which could partially restore budding proficiency. These results show that leucine401 together with the previously identified tyrosine399 form a motif that is required for budding.