In situ high-energy synchrotron radiation study of sol-gel nanoparticle formation in supercritical fluids.
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Biomedical subjects
Publications and source records attributed to Henrik Jensen.
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CE frontal analysis (CE-FA) has been established as a powerful tool to study noncovalent interactions between macromolecules and small molecules such as drug substances or pharmaceutical excipients. However, when using traditional commercial CE instrumentation, a serious drawback is related to the fact that only UV-active compounds can be studied. In recent years, contactless conductivity detection has become an attractive alternative to UV detection in CE due to its high versatility. In this study, we combine contactless conductivity detection and UV detection in a highly versatile setup for profiling noncovalent interactions between low-molecular-weight molecules and macromolecules. In the case of molecules having a chromophore the setup allows determination of binding constants using two independent detectors. The new contactless conductivity detection cell is compatible with commercial CE instrumentation and is therefore easily implemented in any analysis laboratory with CE expertise.
OBJECTIVES: In situations with vaccination coverage high enough to control pertussis, observational studies have reported divergent effects of diphtheria-tetanus-pertussis (DTP) vaccination on childhood survival. We examined whether this could be because of methodological differences. METHODS: Some studies of the impact of DTP updated information on vaccination retrospectively (retrospective updating approach) while others kept vaccination status fixed for the time between follow-up visits (landmark approach). First, we conducted simulations with these approaches to investigate the impact of different mortality levels, vaccination incidence rates, intervals between data collection visits, and the proportion of children whose vaccination card had not been seen after death. Second, we re-analysed data from Guinea-Bissau using the retrospective updating approach. RESULTS: In simulations, the retrospective updating approach produced rate ratio (vaccinated/unvaccinated) estimates biased towards zero because of a differential misclassification which created survival bias as risk-free observation time was allocated to the vaccinated group. The landmark approach produced rate ratio estimates biased towards one. Biases increased with interval between data collection visits and incidence of vaccination, but were unaffected by the underlying mortality level. Survival bias increased with the proportion of dead children whose vaccination status could not be updated. The re-analysis of data from Guinea-Bissau changed the estimated impact of DTP from an 84% higher mortality using the landmark approach to a 37% lower mortality using the retrospective updating approach. CONCLUSIONS: The apparent contradiction between DTP studies could be because of methodological differences. To assess child survival associated with routine vaccinations, studies minimizing the effect of biases are warranted.
BACKGROUND: Observational studies of diphtheria-tetanus-pertussis (DTP) vaccine from longitudinal study sites have reported divergent effects on child survival, ranging from 10-fold reduction to threefold increased mortality. None of these studies had complete information on DTP vaccinations from both survivors and children who died. We reviewed the data analysis methodology to assess whether methodological differences could explain the divergent results. DESIGN: Studies have used case-control design, survival analysis with interval-fixed vaccination status (landmark approach), and survival analysis with retrospective updating of vaccination status. RESULTS: Seven studies using a case-control design or a landmark approach found a negative effect of DTP on child survival. Eight of nine survival analyses with retrospective updating of vaccination status reported a beneficial effect. This beneficial effect of DTP increased with the length of the interval between data collection visits. Studies with long interval between visits had very high mortality rates among unvaccinated children, low mortality rate ratios for vaccinated compared with unvaccinated children, and strongly beneficial estimates of DTP. CONCLUSION: The divergent results in observational studies of the impact of DTP on child survival are partly because of methodological differences. To assess the impact on mortality of routine vaccinations, observational study designs which minimize the effect of bias are warranted. Randomized trials should be considered.
BACKGROUND: Live vaccines including BCG and measles may have non-targeted beneficial effects on childhood survival in areas with high mortality. The authors therefore undertook a survey of vaccinia scars to evaluate subsequent mortality. SUBJECTS: Based on a population census, a cohort of 1893 adults in urban Guinea-Bissau was examined in 1998 and followed until 2002. MAIN OUTCOME MEASURE: All cause mortality, excluding accidents. RESULTS: The median age of vaccinia vaccinations had been 16-18 years. Adults with a vaccinia scar had a mortality ratio (MR) of 0.60 (0.41-0.87) compared to those without any scar. The effect was stronger for women. Mortality decreased with each additional vaccinia scar (MR=0.73 (0.56-0.95)). Among 502 individuals with information on HIV infection, the age-adjusted HIV-2 prevalence was 2.45 (1.06-5.65) for those with a vaccinia scar. Control for district, ethnic group, schooling, place of birth, quality of housing and HIV status had little effect on the estimate. Since vaccinia and BCG scars could have been confused, mortality for adults with vaccinia and/or BCG scar was compared to those without, the MR being 0.61 (0.41-0.89). CONCLUSION: Known cultural or socio-economic factors possibly associated with access to vaccination had no influence on the mortality ratio for having a vaccinia scar. Hence, vaccinia vaccination may have a prolonged beneficial effect on adult survival.
BACKGROUND: According to studies from Guinea-Bissau and Senegal, live vaccines may reduce the female-male mortality ratio (MR) whereas inactivated vaccines increase this ratio. We used data from The Gambia to examine whether similar tendencies could be found in a different setting. SETTING: Forty villages in the Farafenni area in rural Gambia. SUBJECTS: A population of 17,000 was followed with demographic surveillance between 1998 and 2002; 537 children less than 5 years of age died in this period. METHODS: We used two vaccination surveys and community mortality data to examine, first, the female-male mortality ratio (MR) in the age groups in which DTP and MV are recommended and have a high coverage. Second, using vaccination cards seen post-mortem, we examined the distribution of live or inactivated vaccines as last vaccination in different age groups. Third, we examined the effect of DTP and MV administered simultaneously. MAIN OUTCOME MEASURES: The female-male MR in different age groups and for different vaccines. RESULTS: Vaccination coverage was high for BCG, third dose of DTP (DTP3) and MV, reaching a level of 80-90% within a few months of the recommended age of vaccination. First, the female-male MR was 0.93 (0.63-1.38) in the first 2 months of life when children had received no vaccination or the combination of BCG, HBV and OPV. From 2 to 8 months of age, with DTP and HBV being the main vaccinations, the female-male MR was 1.28 (0.86-1.89). Between 9 and 17 months of age, with MV as the main vaccination, this ratio dropped to 0.73 (0.50-1.07), a significant inversion of the female-male MR (p=0.045). Second, using information from vaccination cards of dead children, boys who died at 2-4 months of age were more likely to have received live BCG and girls to have received inactivated DTP and HBV as last vaccination (p<0.001). At 5-8 months of age, essentially all dead children had received DTP as last vaccination and the female-male MR was 1.68 (0.96-2.93), whereas the MR was 0.70 (0.43-1.15) at 12-17 months of age when nearly all dead children had received MV (p=0.022). Third, compared with the general population of children who had received MV, dead children who had received MV were more likely to have received DTP3 simultaneously with MV (relative risk (RR)=5.59 (2.10-14.8)) or after MV (RR=2.61 (1.13-6.05)). CONCLUSION: Most children dying at a specific age had received the recommended vaccines. BCG and MV as last vaccination was associated with a low female-male MR, whereas DTP as last vaccination was associated with a high female-male MR. These trends are consistent with observations from other African countries.
OBJECTIVE: West African studies have hypothesized that increased female mortality after high-titre measles vaccine (HTMV) was due to subsequent diphtheria-tetanus-pertussis (DTP) and inactivated polio vaccine (IPV) vaccinations. We tested two deductions from this hypothesis in HTMV studies from rural Sudan and Kinshasa; first, there should be no excess female mortality for HTMV recipients when DTP was not given after HTMV and second, excess female mortality should only be found among those children who received DTP after HTMV. STUDIES: The Sudanese trial randomised 510 children to Edmonston-Zagreb (EZ) HTMV, Connaught HTMV or a control vaccine (meningococcal). Both the Connaught HTMV and the control group received standard measles vaccine at 9 months. In the Kinshasa study 1023 children received one dose of HTMV at 6 months or two doses at 312 and 912 months of age. FINDINGS: First, the Sudan trial is one of the few randomised studies of measles vaccine; the EZ HTMV group had lower mortality between 5 and 9 months of age than controls, the mortality ratio (MR) being 0.00 (p = 0.030). This effect was not due to prevention of measles infection. Second, both studies provided evidence that HTMV per se was associated with low mortality. In a combined analysis comparing both HTMV groups with controls, the HTMV groups had a MR of 0.09 (0.01-0.71) between 5 and 9 months of age. In Kinshasa, the HTMV recipients who did not receive simultaneous DTP had an annual mortality rate of only 1.0% between 6 months and 3 years of age. Third, the female-male MR was related to subsequent DTP vaccinations. In Kinshasa, the female-male MR was only 0.40 (0.13-1.27) among the HTMV recipients who did not receive further doses of DTP. In Sudan, the female-male mortality ratio in the EZ group was 3.89 (95% CI 1.02-14.83) and the female-male MR increased with number of doses of DTP likely to have been given during follow-up (trend, p = 0.043). Fourth, in Kinshasa, mortality was higher among children who had received HTMV and DTP simultaneously than among children who had received HTMV alone (MR = 5.38 (1.37-21.2)). CONCLUSIONS: Measles vaccine is associated with non-specific beneficial effects. When not given with DTP, HTMV per se was associated with low mortality. Increased female mortality was not found among children who did not receive DTP after HTMV. Hence, our deductions were supported and the sequence or combination of vaccinations may have an effect on sex-specific mortality patterns in low-income countries.
OBJECTIVE: To identify prognostic risk factors in patients with occupational hand eczema (OHE). DESIGN: Cohort study with 1-year follow-up. SETTING: Danish National Board of Industrial Injuries Registry. PATIENTS: All patients with newly recognized OHE (758 cases) from October 1, 2001, through November 10, 2002. INTERVENTIONS: Participants received a questionnaire covering self-rated severity, sick leave, loss of job, depression, and health-related quality of life. One year after the questionnaire was returned, all responders (N = 621) received a follow-up questionnaire, and 564 (91%) returned it. MAIN OUTCOME MEASURES: Persistently severe or aggravated OHE, prolonged sick leave, and loss of job after 1-year follow-up. RESULTS: During the follow-up period, 25% of all patients with OHE had persistently severe or aggravated disease, 41% improved, and 34% had unchanged minimal or mild to moderate disease. Patients with atopic dermatitis fared poorly compared with other patients. Patients younger than 25 years fared clearly better than older groups. Furthermore, severe OHE, age 40 years or greater, and severe impairment of quality of life at baseline appeared to be important predictors of prolonged sick leave and unemployment. Patients with lower socioeconomic status also had a high risk of prolonged sick leave, job change, and loss of job. Contact allergy was not found to be a risk factor for poor prognosis. CONCLUSIONS: Atopic dermatitis, greater age, and low socioeconomic status may be reliable prognostic factors in early OHE. Quality of life and standardized severity assessment may also be valuable tools to identify patients at high risk of prolonged sick leave and unemployment.
BACKGROUND AND PURPOSE: Inline ultrasound monitoring requires good image quality for accurate stone localization, as well as low shockwave shadowing and a robust transducer. In general, conventional transducers designed for another purpose, such as abdominal scanning, are employed. The distance between the transducer and the SWL focus can be varied by a mechanical drive. The drawback is reduced fragmentation at short distances and poor imaging at long distances. This paper introduces a new approach using a specially designed transducer without a mechanical drive. MATERIALS AND METHODS: A transducer prototype with optimized beam focusing (B-K Medical, Herlev, Denmark) was integrated into a modified Compact Delta II therapy head (Dornier MedTech, Wessling, Germany). Image quality was tested at two clinical sites, where 40 kidney and 14 ureteral stones were treated. The shockwave was characterized by model stone tests and fiberoptic hydrophone measurements. RESULTS: Both kidney and ureteral stone treatments could be monitored reliably. Despite the long distance to the SWL focus, the transducer could be operated with relatively high frequencies (3.5-6 MHz), so that high image resolution was obtained. Model stone tests yielded the same fragmentation as the standard Compact Delta II without a transducer. CONCLUSIONS: This study shows that the concept of an integrated transducer distant from the shockwave focus is feasible. Transducer elevation, which is accompanied by shockwave shadowing and early transducer failure, is avoided by employing a dedicated transducer design.
BACKGROUND: Recent studies have suggested that bacille Calmette-Guérin (BCG) immunization may have a nonspecific beneficial effect on infant survival and that the effect may be more pronounced among girls. In a prospective birth cohort, we examine whether a positive tuberculin skin test and BCG scar in response to BCG immunization were related to better overall survival in Guinea-Bissau and, if so, whether the effect was sex-specific. METHODS: Skin tests and BCG scarring were monitored at ages 2 months (n = 2332) and 6 months (n = 1817) in children born from March 2000 to July 2002. A tuberculosis (TB) surveillance system allowed us to exclude from the analysis children with likely TB exposure. The children were followed for survival until 18 months of age. RESULTS: Among children with a tuberculin skin test at 2 and 6 months of age, the mortality rate ratio for skin test reactors (>1 mm) versus nonreactors (0-1 mm) was 0.54 (95% confidence interval = 0.30-0.99). Comparing children with and without a BCG scar, the ratio was 0.55 (0.31-0.96). The effect of a skin test reaction or a BCG scar seemed stronger among girls; for those with positive reaction, the mortality ratio was 0.31 (0.11-0.88) among girls and 0.84 (0.39-1.82) among boys; and for BCG scar, the results were 0.41 (0.21-0.82) and 0.88 (0.34-2.30), respectively. CONCLUSIONS: A good response to BCG vaccination is related to lower child mortality. The effect seems most pronounced among girls. The findings may have implications for future vaccine trials and policy.
BACKGROUND: Recent studies from West Africa suggest that routine vaccinations may have sex differential nontargeted effects. To answer whether these patterns are found elsewhere, we reanalyzed data about vaccinations and mortality in a Malawian cohort. METHODS: Children were followed from birth with monthly home visits until 18 months of age. Anthropometric measurements and vaccination information were obtained at these visits. We investigated survival in relation to vaccination status using 2 different methods. First, we included all children updating vaccination information retrospectively. Second, we included only those present at monthly home visits for whom prospective vaccination information was likely to be most complete. SUBJECTS: This study included 751 children surviving the first week of life. MAIN OUTCOME MEASURES: Main outcome measures consisted of mortality rate ratios (MR) for BCG, diphtheria-tetanus-pertussis (DTP) and measles-vaccinated children compared with children who had not received these vaccines and female-male MRs among children who had received the same vaccine. RESULTS: In all analyses, BCG and MV were associated with lower mortality. Children with better nutritional status received DTP1 significantly earlier (P = 0.02). However, DTP1-vaccinated children did not have lower mortality, the MR being 0.99 (0.45-2.19) and 3.19 (0.80-12.8), respectively, using the 2 analyses with retrospective updating or with prospective determination of vaccination status. The female-male MR varied significantly with age, being increased at 3 to 8 months of age, the age of DTP vaccination, and reduced between 9 and 17 months of age, the age of measles vaccination (MV). Using prospective vaccination information, the MR for girls declined after BCG vaccination of unvaccinated girls but increased after DTP1 (P = 0.10) and declined after MV (P = 0.01). Children who received DTP and MV simultaneously had a MR of 5.27 (1.11-25.0) compared with children who received MV only. CONCLUSION: The female-male mortality ratio varied with age. The mode of analysis was important. Using prospective vaccination information like in previous studies from West Africa, BCG, DTP1 and MV had differential effects for girls and boys.
Occupational hand eczema (OHE) is the most frequently recognized occupational disease in Denmark, and despite governmental attempts to reduce exposure to harmful occupational allergens, the number of new cases has remained almost unchanged since the mid-1990s. Some studies have indicated that OHE has considerable impact on quality of life (QoL) and may lead to depression. The aims of the study were to determine risk factors for low QoL, the frequency and severity of depression among OHE patients and changes in QoL and depression after 12 months of follow up. The study population, 758 patients, comprised all new recognized cases from the Danish National Board of Industrial Injuries Registry between October 2001 and November 2002. All patients received a questionnaire to determine impairment of QoL and depressive symptoms. A similar follow-up questionnaire was posted after 1 year. The response rate was 82% at baseline and 91% at follow up. The mean Dermatology Life Quality Index total score was 5.5 for all patients and 7.8 for severe OHE cases. Severe OHE cases and lower socioeconomic status were independently associated with low QoL. The prevalence of moderate-to-severe depression was 9%. Only minor changes in QoL and depressive symptoms were found after 12 months of follow up.
1. Here we examine how sex ratio variation in house sparrow broods interacts with other demographic traits and parental characteristics to improve the understanding of adaptive significance and demographic effects on variation in sex ratio. 2. The sex ratio in complete broods did not deviate significantly from parity (54.9% males). 3. There was sex-specific seasonal variation in the probability of recruitment. Male nestlings that hatched late in the breeding season had larger probability of surviving than early hatched males. 4. An adaptive adjustment of sex ratio should favour production of an excess of males late in the breeding season. Accordingly, the proportion of male offspring increased throughout the breeding season. 5. A significant nonlinear relationship was present between sex ratio and age of the female. However, there was no relationship between parental phenotype and standardized hatch day that could explain the observed seasonal change in sex ratio. 6. The sex-specific number of offspring recruited by a pair to subsequent generations was closely related to the brood sex ratio. 7. These results indicate an adaptive adjustment of sex ratio to seasonal variation in environmental conditions that affects the offspring fitness of the two sexes differently. Our results also suggest that such a sex ratio variation can strongly influence the demography and structural composition of small passerine populations.
In conservation ecology there is an urgent need for indicators that can be used to predict the risk of extinction of populations. Identifying extinction-prone populations has been difficult because few data sets on the demographic characteristics of the final stage to extinction are available and because of problems in separating out stochastic effects from changes in the expected dynamics. We documented the demographic changes that occurred during the period prior to extinction of a small island population of House Sparrows (Passer domesticus) after the end of permanent human settlement. A mark-recapture analysis revealed that this decline to extinction was mainly due to increased mortality after closure of the last farm that resulted in a negative long-term-specific growth rate. No change occurred in either the structural composition (breeding sex ratio and age distribution) of the population or in female recruitment. No male, however, recruits were produced on the island after the farm closure. Based on a simple, stochastic, density-dependent model we constructed a population prediction interval (PPI) to estimate the time to extinction. The 95% PPI slightly overestimated the time to extinction with large uncertainty in predictions, especially due to the influence of demographic stochasticity and parameter drift. Our results strongly emphasize the importance of access to data on temporal variation that can be used to parameterize simple population models that allow estimation of critical parameters for credible prediction of time to extinction.
OBJECTIVES: This study examined whether atopic disposition, wheezing, and atopic disorders increased the risk of hospitalizations because of respiratory syncytial virus in children between birth and 18 months of age. PATIENTS AND METHODS: Relative risks for respiratory syncytial virus hospitalization were studied in a nested 1:5 case-control design using exposure information obtained from interviews with mothers of 2564 case and 12,816 control children who had been followed prospectively from birth and until 18 months of age as participants in the Danish National Birth Cohort. Information on the children's ages at respiratory syncytial virus hospitalization, presentation of infrequent wheezing, recurrent wheezing, and atopic dermatitis were used to study these associations chronologically. RESULTS: The adjusted relative risk of respiratory syncytial virus hospitalization in the offspring was 1.11 for maternal atopic dermatitis, 1.72 for maternal asthma, and 1.23 for paternal asthma. Atopic dermatitis in the child was associated with an increased risk of subsequent respiratory syncytial virus hospitalization among infants <6 months of age. Infrequent wheezing was associated with a relative risk of subsequent respiratory syncytial virus hospitalization of 2.98 and recurrent wheezing with a relative risk of 5.90. These associations were present also if infants with medical risk factors were excluded from the analysis. CONCLUSIONS: Asthmatic disposition and wheezing were strong determinants of subsequent respiratory syncytial virus hospitalization in Danish children <18 months of age.
BACKGROUND: The crude mortality rate of the whole population and the mortality of children <5 years of age are the common indicators of the severity of a complex emergency situation. However, these indicators rarely take account of differences in socioeconomic conditions and vulnerability. METHODS: We followed a population in Guinea-Bissau, which fled when fighting took place in the capital during the war in 1998-99. The population stayed close to the area of conflict and returned as soon as a cease-fire was negotiated. A peace treaty was signed after half-a-year. The following 6 months was a period of returning and re-settlement, even though two outbreaks of fighting occurred. RESULTS: In the first half-year the mortality rate was 78% [mortality ratio (MR) = 1.78; 95% CI 1.61-1.97] increased and mortality for children <5 years of age doubled (MR = 2.07; 95% CI 1.79-2.38). In the last 6 months of the war, mortality was slightly increased for children and not at all for the total population. In the first half-year, households living in better houses and having members with schooling were less affected. In the 're-settlement' period two inequalities emerged; the largest ethnic group, Pepel, continued to have high mortality when the mortality of other groups declined; likewise girls continued to have an elevated mortality whereas mortality of boys declined. CONCLUSION: Whereas specific 'free' interventions reduced social inequalities for the groups affected, for the total population health-inequalities were slightly amplified during the war. Once the population returned to their urban homes, mortality fell to pre-war levels even though some fighting continued, limited humanitarian aid was available and the pre-war infra-structure had not been re-established.
OBJECTIVES: To determine whether the dose of vitamin A currently recommended by the World Health Organization or half this dose gives better protection against childhood morbidity and mortality. DESIGN: Randomised study. SETTING: A combined oral polio vaccine and vitamin A supplementation campaign in Guinea-Bissau, Africa. PARTICIPANTS: 4983 children aged 6 months to 5 years. INTERVENTIONS: One of two doses of vitamin A (recommended and half); oral polio vaccine. MAIN OUTCOME MEASURES: Mortality and morbidity at six and nine months. RESULTS: Mortality was lower in the children who took half the recommended dose of vitamin A compared with the full dose at both six months (mortality rate ratio 0.69, 95% confidence interval 0.36 to 1.35) and nine months (0.62, 0.36 to 1.06) of follow-up. There was a significant interaction between sex and dose, the lower dose being associated with significantly reduced mortality in girls (0.19, 0.06 to 0.66) but not in boys (1.98, 0.74 to 5.29). The lower dose of vitamin A was consistently associated with lower hospital case fatality in girls (0.19, 0.02 to 1.45). Paradoxically, in children aged 6-18 months, the low dose was associated with slightly higher morbidity. CONCLUSIONS: Half the dose of vitamin A currently recommended by WHO may provide equally good or better protection against mortality but not against morbidity.
This work addresses two ways of loading proteins on microchannel surfaces for immunoassay applications: the "stop-flow" and the continuous flow processes. The "stop-flow" method consists of successive static incubation periods where the bulk solution depletes upon the adsorption process. In the present paper, a multi-step "stop-flow" protein coating is studied and compared to a coating under continuous flow conditions. For the "stop-flow", a non-dimensional parameter is here introduced, indicating the adsorbing capacity of the system, by which it is possible to calculate the number of loads necessary to reach the optimum coverage. For the continuous flow, the effects on the adsorption of the kinetic rates, flow velocity and wall capacity have been considered. This study shows the importance of a careful choice of the fluid velocity to minimise the sample waste. For diffusion controlled and kinetics controlled processes, two flow velocity criteria are provided in order to obtain the best possible coverage, with the same amount of sample as with the "stop-flow".