Francisella tularensis is one of the most infectious human pathogens known. In the past, both the former Soviet Union and the US had programs to develop weapons containing the bacterium. We report the complete genome sequence of a highly virulent isolate of F. tularensis (1,892,819 bp). The sequence uncovers previously uncharacterized genes encoding type IV pili, a surface polysaccharide and iron-acquisition systems. Several virulence-associated genes were located in a putative pathogenicity island, which was duplicated in the genome. More than 10% of the putative coding sequences contained insertion-deletion or substitution mutations and seemed to be deteriorating. The genome is rich in IS elements, including IS630 Tc-1 mariner family transposons, which are not expected in a prokaryote. We used a computational method for predicting metabolic pathways and found an unexpectedly high proportion of disrupted pathways, explaining the fastidious nutritional requirements of the bacterium. The loss of biosynthetic pathways indicates that F. tularensis is an obligate host-dependent bacterium in its natural life cycle. Our results have implications for our understanding of how highly virulent human pathogens evolve and will expedite strategies to combat them.

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Summary Background Crohn's disease (CD) is a predisposing factor for bone loss and muscle dysfunction, which could lead to osteoporotic fractures and physical disability, respectively. Aim To assess the effect of 6 months of combined impact and resistance training on bone mineral density (BMD) and muscle function in adults with CD. Methods In this randomised controlled trial, 47 adults with stable CD were assigned to exercise (n = 23) or control (n = 24) groups and followed up for 6 months. The exercise group received usual care plus a 6‐month combined impact and resistance training programme, involving three, 60‐minute sessions per week and a gradual tapering of supervision to self‐management. The control group received usual care alone. The primary outcomes were BMD (via dual energy X‐ray absorptiometry) and muscle function (measures of upper and lower limb strength and endurance) at 6 months. Results At 6 months, BMD values were superior in the exercise group with statistical significance at lumbar spine (adjusted mean difference 0.036 g/cm2, 95% CI 0.024‐0.048; P < 0.001), but not at femoral neck (0.018 g/cm2, 0.001‐0.035; P = 0.059) or greater trochanter (0.013 g/cm2, −0.019 to 0.045; P = 0.415) after correcting for multiple outcomes. The exercise group also had superior values for all muscle function outcomes (P < 0.001; unadjusted mean differences ranging 22.6‒48.2%), and lower fatigue severity (P = 0.005). Three exercise‐related adverse events were recorded: two instances of light‐headedness and one of nausea. Conclusions The intervention improved BMD and muscle function in adults with CD and appears as a suitable model of exercise for reducing future risk of osteoporotic fractures and disability. Trial registration: ISRCTN11470370.

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Initiation was characterized as ubiquitous in terms of peer networks' use and availability. Because of the prevalent norm of MA use, these data indicate that interventions targeting social networks and young Thais before MA initiation are needed.

Alcohol related liver disease, haemat-ological disease, renal failure and neoplasia are much more common causes of marked hyperferritinaemia than haemochromatosis. The role of weight loss in hyperferritinaemia may warrant further investigation.

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