Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950–1963: an epidemiological analysis of historical data

Background Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening. Methods and findings Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing. Conclusions A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today’s high tuberculosis burden countries and with new screening tools and technologies

Designing a broad-spectrum integrative approach for cancer prevention and treatment

Targeted therapies and the consequent adoption of "personalized" oncology have achieved notablesuccesses in some cancers; however, significant problems remain with this approach. Many targetedtherapies are highly toxic, costs are extremely high, and most patients experience relapse after a fewdisease-free months. Relapses arise from genetic heterogeneity in tumors, which harbor therapy-resistantimmortalized cells that have adopted alternate and compensatory pathways (i.e., pathways that are notreliant upon the same mechanisms as those which have been targeted). To address these limitations, aninternational task force of 180 scientists was assembled to explore the concept of a low-toxicity "broad-spectrum" therapeutic approach that could simultaneously target many key pathways and mechanisms. Using cancer hallmark phenotypes and the tumor microenvironment to account for the various aspectsof relevant cancer biology, interdisciplinary teams reviewed each hallmark area and nominated a widerange of high-priority targets (74 in total) that could be modified to improve patient outcomes. For thesetargets, corresponding low-toxicity therapeutic approaches were then suggested, many of which werephytochemicals. Proposed actions on each target and all of the approaches were further reviewed forknown effects on other hallmark areas and the tumor microenvironment. Potential contrary or procar-cinogenic effects were found for 3.9% of the relationships between targets and hallmarks, and mixedevidence of complementary and contrary relationships was found for 7.1%. Approximately 67% of therelationships revealed potentially complementary effects, and the remainder had no known relationship. Among the approaches, 1.1% had contrary, 2.8% had mixed and 62.1% had complementary relationships. These results suggest that a broad-spectrum approach should be feasible from a safety standpoint. Thisnovel approach has potential to be relatively inexpensive, it should help us address stages and types ofcancer that lack conventional treatment, and it may reduce relapse risks. A proposed agenda for futureresearch is offered

The effects of in vivo exposure to cadmium, copper and zinc on the activities of gill ATPases in the Norway lobster, Nephrops norvegicus

PubMedID: 8975822Norway lobsters, Nephrops norvegicus were exposed for 18 days to combinations of cadmium, copper and zinc at three sublethal concentrations (1, 5, 25 µg/L for Cd and Cu, and 8, 40 and 200 µg/L for Zn). Male animals were exposed to all three concentrations, while female animals were studied only in one (highest) concentration of the metals. Activities of Na,K-ATPase and both oligomycin-sensitive and insensitive Mg-ATPase were investigated in relation to metal exposure. A group of male Nephrops of different size groups from a single location in the Clyde Sea was also sampled to investigate the relationship between size and ATPase activity. Cadmium concentrations increased significantly with increases in exposure concentrations in both male and female animals, whereas copper and zinc increased significantly only in the highest treatment in males. There was no significant difference in concentrations of the metals in control male and female animals, whereas males accumulated significantly higher levels of copper and zinc in the highest concentrations of the metals. Control males showed higher activity of Na,K-ATPase than control females. Na,K-ATPase activity was significantly inhibited in male animals exposed to metals whereas in female animals there was only a significant inhibition in total Mg-ATPase activity. Na,K-ATPase activity had a negative relationship with copper in males, while in treated females this ATPase had positive relationship with zinc and copper. There were negative relationships between the activities of Na,K-ATPase and oligomycin sensitive Mg-ATPase with carapace length of the animals

The induction of metallothionein in tissues of the Norway lobster Nephrops norvegicus following exposure to cadmium, copper and zinc: The relationships between metallothionein and the metals

Nephrops norvegicus were exposed simultaneously to cadmium, copper and zinc over an 18-day, period. Exposure concentrations were control, 1, 5 and 25 µg litre-1 for cadmium and copper and 8, 40 and 200 µg litre-1 for zinc. Concentrations of cadmium, copper, zinc and metallothionein were measured in homogenates of both the gill and the hepatopancreas. Quantification of metallothionein was carried out by differential pulse polarography. Cadmium concentrations increased significantly in the gill and hepatopancreas of both male and female animals in response to increases in exposure concentration. In contrast, the concentration of copper and zinc increased significantly in the gills of males, but not in females. In the hepatopancreas, neither copper nor zinc resulted in significant changes in concentrations of these metals. Metallothionein concentrations in the gill and hepatopancreas were increased significantly in relation to metal exposure in both males and females. Concentrations of cadmium and metallothionein in both the gill and hepatopancreas of males and females were positively correlated. Copper in the hepatopancreas also showed positive relationships with MT concentrations in males, but not in females. This study suggested that cadmium MTs in the gill and hepatopancreas of Nephrops norvegicus could be used as a sensitive tool to detect cadmium contamination in the lobsters, although this was not true for copper and zinc

Growth and osmoregulation in Salmo salar L. juveniles 1+, 1½ + and 2+ reared under restrained salinity

The freshwater phase of Atlantic salmon Salmo salar L vary between one and eight years. The reduction of the freshwater phase is desirable to reduce freshwater usage, human resources and to increase year round availability of pan-sized salmon. Three trials were conducted to investigate the possibility of supply the market in a year-round basis, with pan-sized Atlantic salmon Salmo salar L. (250-300 g) in Portugal (southern limit of the natural distribution of this species). This study primarily aimed to compare the osmoregulatory ability and growth of different fish sizes, smolts 1+ (trial 1), 1.5+ (trial 2) and 2+ (trial 3), in freshwater and seawater conditions. Additionally, effects of photoperiod were determined in smolts 1.5+ (trial 2) for both freshwater and seawater groups. The increments in the plasma osmolality and chlorine concentrations after seawater transfer suggest an identical development in the hypo-osmoregulation capacity among the different age classes. In all trials, weight gain was smaller after 30 d of saltwater transfer when compared to fish reared in freshwater. However, the growth depression was temporary. Seawater group showed a compensatory growth in the immediate months, which permitted an improvement in growth rates. At the end of trials there were minor differences on growth performance between freshwater and seawater groups. Specific growth rates varied between 0.7 and 1.0 % day-1, according to the age and /or size and transfer season