Sequential ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) scan findings in patients with extrapulmonary tuberculosis during the course of treatment—a prospective observational study

BACKGROUND: Initial studies of tuberculosis (TB) in macaques and humans using ¹⁸F-FDG positron emission tomography (PET) imaging as a research tool suggest its usefulness in localising disease sites and as a clinical biomarker. Sequential serial scans in patients with extrapulmonary TB (EPTB) could inform on the value of PET-CT for monitoring response to treatment and defining cure. PATIENTS AND METHODS: HIV-negative adults with EPTB from eight sites across six countries had three ¹⁸F-FDG PET/CT scans: (i) within 2 weeks of enrolment, (ii) at 2 months into TB treatment and (iii) at end of ATT treatment. Scanning was performed according to the EANM guidelines. ¹⁸F-FDG PET/CT scans were performed 60 ± 10 min after intravenous injection of 2.5–5.0 MBq/kg of ¹⁸F-FDG. FINDINGS: One hundred and forty-seven patients with EPTB underwent 3 sequential scans. A progressive reduction over time of both the number of active sites and the uptake level (SUVmax) at these sites was seen. At the end of WHO recommended treatment, 53/147 (36.0%) patients had negative PET/CT scans, and 94/147 (63.9%) patients remained PET/CT positive, of which 12 patients had developed MDR TB. One died of brain tuberculoma. INTERPRETATION: Current ⁸F-FDG PET/CT imaging technology cannot be used clinically as a biomarker of treatment response, cure or for decision-making on when to stop EPTB treatment. PET/CT remains a research tool for TB and further development of PET/CT is required using new Mycobacterium tuberculosis-specific radiopharmaceuticals targeting high-density surface epitopes, gene targets or metabolic pathways

PET/CT features of extrapulmonary tuberculosis at first clinical presentation: a cross-sectional observational ¹⁸F-FDG imaging study across six countries

BACKGROUND: A large proportion of the huge global burden of Extrapulmonary tuberculosis (EPTB) are treated empirically without accurate definition of disease sites, and extent of multi-organ disease involvement. Positron emission tomography (PET) imaging using 18F-FDG in TB could be a useful imaging technique for localising disease sites and extent of disease. METHODS: We conducted a study of HIV-negative adult patients with a new clinical diagnosis of EPTB across 8 centres located in 6 countries: India, Pakistan, Thailand, South Africa, Serbia, and Bangladesh to assess the extent of disease and common sites involved at first presentation. 18F-FDG PET/CT scans were performed within 2 weeks of presentation. FINDINGS: A total of 358 patients with EPTB (189 females; 169 males) were recruited over 45 months. Age range 18-83 years (females: median 30 years; males: median 38 years). 350/358 (98%) patients (183 female, 167 male) had positive scan. 118/350 (33.7%) had a single extrapulmonary site and 232/350 (66.3%) had more than one site (organ) affected. Lymph nodes, skeletal, pleura and brain were common sites. 100/358 (28%) of EPTB patients had 18F-FDG PET/CT positive sites in the lung. 110 patients were 18F-FDG PET/CT positive in more body sites than were noted clinically at first presentation and 160 patients had the same number of positive body sites. INTERPRETATION: 18F-FDG PET/CT scan has potential for further elucidating the spectrum of disease, pathogenesis of EPTB, and monitoring the effects of treatment on active lesions over time, and requires longitudinal cohort studies, twinned with biopsy and molecular studies

Evidence for sparse synergies in grasping actions

Converging evidence shows that hand-actions are controlled at the level of synergies and not single muscles. One intriguing aspect of synergy-based action-representation is that it may be intrinsically sparse and the same synergies can be shared across several distinct types of hand-actions. Here, adopting a normative angle, we consider three hypotheses for hand-action optimal-control: sparse-combination hypothesis (SC) – sparsity in the mapping between synergies and actions - i.e., actions implemented using a sparse combination of synergies; sparse-elements hypothesis (SE) – sparsity in synergy representation – i.e., the mapping between degrees-of-freedom (DoF) and synergies is sparse; double-sparsity hypothesis (DS) – a novel view combining both SC and SE – i.e., both the mapping between DoF and synergies and between synergies and actions are sparse, each action implementing a sparse combination of synergies (as in SC), each using a limited set of DoFs (as in SE). We evaluate these hypotheses using hand kinematic data from six human subjects performing nine different types of reach-to-grasp actions. Our results support DS, suggesting that the best action representation is based on a relatively large set of synergies, each involving a reduced number of degrees-of-freedom, and that distinct sets of synergies may be involved in distinct tasks

Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: Evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre.

QUESTION: Does Nitisinone prevent the clinical progression of the Alkaptonuria? FINDINGS: In this observational study on 39 patients, 2 mg of daily nitisinone inhibited ochronosis and significantly slowed the progression of AKU over a three-year period. MEANING: Nitisinone is a beneficial therapy in Alkaptonuria. BACKGROUND: Nitisinone decreases homogentisic acid (HGA), but has not been shown to modify progression of Alkaptonuria (AKU). METHODS: Thirty-nine AKU patients attended the National AKU Centre (NAC) in Liverpool for assessments and treatment. Nitisinone was commenced at V1 or baseline. Thirty nine, 34 and 22 AKU patients completed 1, 2 and 3 years of monitoring respectively (V2, V3 and V4) in the VAR group. Seventeen patients also attended a pre-baseline visit (V0) in the VAR group. Within the 39 patients, a subgroup of the same ten patients attended V0, V1, V2, V3 and V4 visits constituting the SAME Group. Severity of AKU was assessed by calculation of the AKU Severity Score Index (AKUSSI) allowing comparison between the pre-nitisinone and the nitisinone treatment phases. RESULTS: The ALL (sum of clinical, joint and spine AKUSSI features) AKUSSI rate of change of scores/patient/month, in the SAME group, was significantly lower at two (0.32 ± 0.19) and three (0.15 ± 0.13) years post-nitisinone when compared to pre-nitisinone (0.65 ± 0.15) (p < .01 for both comparisons). Similarly, the ALL AKUSSI rate of change of scores/patient/month, in the VAR group, was significantly lower at one (0.16 ± 0.08) and three (0.19 ± 0.06) years post-nitisinone when compared to pre-nitisinone (0.59 ± 0.13) (p < .01 for both comparisons). Combined ear and ocular ochronosis rate of change of scores/patient/month was significantly lower at one, two and three year's post-nitisinone in both VAR and SAME groups compared with pre-nitisinone (p < .05). CONCLUSION: This is the first indication that a 2 mg dose of nitisinone slows down the clinical progression of AKU. Combined ocular and ear ochronosis progression was arrested by nitisinone

Data on items of AKUSSI in Alkaptonuria collected over three years from the United Kingdom National Alkaptonuria Centre and the impact of nitisinone.

Alkaptonuria is a rare genetic disorder characterized by a high level of circulating (and urine) homogentisic acid (HGA), which contributes to ochronosis when it is deposited in connective tissue as a pigmented polymer. In an observational study carried out by National AKU Centre (NAC) in Liverpool, a total of thirty-nine AKU patients attended yearly visits in varying numbers. At each visit a mixture of clinical, joint and spinal assessments were carried out and the results calculated to yield an AKUSSI (Alkaptonuria Severity Score Index), see "Nitisinone arrests ochronosis and decreases rate of progression of Alkaptonuria: evaluation of the effect of nitisinone in the United Kingdom National Alkaptonuria Centre" (Ranganath at el., 2018). The aim of this data article is to produce visual representation of the change in the components of AKUSSI over 3 years, through radar charts. The metabolic effect of nitisinone is shown through box plots

Examination of H8 and B8 leadscrews from Three Mile Island Unit 2 (TMI-2)

Visual examinations, preliminary temperature estimates, and chemical and radiological analyses were conducted on samples removed from the control rod drive leadscrews. Hardness measurements and microstructure analysis suggest that significant temperature differences existed between the portions of the leadscrews closest to the bottom and top of the plenum assembly. Preliminary analysis indicates that the temperatures ranged from 666 to 1255/sup 0/K (740 to 1800/sup 0/F) for H8 and 723 to 1033/sup 0/K (842 to 1400/sup 0/F) for B8. The uncertainty in the temperature estimates is about +-28 to 56/sup 0/K (+-50 to 100/sup 0/F). Chemical analyses indicate that UO/sub 2/ and zirconium were deposited to a greater extent on surfaces closer to the core. Radiological analyses suggest that a number of the H8 radionuclides are insoluble in strong acid solutions. In contrast, more of the B8 radionuclides are soluble in strong acidic solutions. Also, an axial gradient in surface radionuclide concentrations was observed, with the highest concentration near the top of the plenum assembly. The data indicate changes in chemical composition and gradients in the surface radionuclide concentrations in the plenum assembly. As extrapolated from leadscrew data, the fractions of total core inventory of radionuclides retained on the plenum assembly surfaces are small (&lt;2%)