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Importance Subclinical hypothyroidism has been associated with heart failure, but no conclusive clinical trial assessed whether treating subclinical hypothyroidism with levothyroxine has an impact on cardiac function. Objective To assess the impact of levothyroxine treatment on cardiac function in subclinical hypothyroidism. Design This is a randomized, double-blind placebo-controlled, multicenter Swiss substudy within the TRUST trial. Participants Participants aged ≥65 years with subclinical hypothyroidism. Intervention Levothyroxine to achieve TSH normalization, or placebo including mock titrations. Main outcome measures Primary outcomes, assessed by echocardiography at the end of the trial were the left ventricular ejection fraction (LVEF, normal defined as >50%) for systolic function and the ratio between mitral peak velocity of early filling (E) to early diastolic mitral annular velocity (e' (E/e' ratio) for diastolic function. Secondary outcomes included transmitral E and A waves, e' lateral/septal, left atrial (LA) volume index and systolic pulmonary artery pressure. Results Of 217 randomized Swiss participants of the TRUST trial, 185 (mean age 74.1 years, 47% women, mean TSH at baseline 6.35 ± SD 1.95 mIU/L) underwent echocardiography. After a median treatment duration of 18.4 months, the mean TSH among participants randomized to levothyroxine (n=95) decreased to 3.55 mIU/L, whereas it remained elevated in the placebo group (n=89; 5.29 mIU/L). The mean LVEF was similar in both arms (adjusted between-group difference 0.4%, 95% CI −1.8% to 2.5%, P=0.72) and no significant differences were found for the E/e' ratio (adjusted between-group difference 0.4, 95% CI −0.7 to 1.4, P=0.47). In intention-to-treat and per-protocol analyses, no clinically significant differences were found for secondary diastolic function parameters: e' lateral 8 vs. 8 cm/s, P=0.54; e' septal 6 vs. 6 cm/s, P=0.75; LA volume index 34 vs. 33 ml/m2, P=0.57; E/A ratio 0.8 vs. 0.8, P=0.94; E deceleration time 225 vs. 216 ms, P=0.27, except for systolic pulmonary artery pressure (37 mm Hg in the levothyoxine group vs. 33 mm Hg in the placebo group, P=0.02 intention-to-treat and P=0.06 per protocol) Conclusion Treatment of subclinical hypothyroidism with levothyroxine was not associated with benefits regarding systolic and diastolic heart function in older adults with subclinical hypothyroidism.

The Vip3 proteins produced during vegetative growth by strains of the bacterium Bacillus 27 thuringiensis show insecticidal activity against lepidopteran insects with a mechanism of action that 28 may involve pore formation and apoptosis. These proteins are promising supplements to our 29 arsenal of insecticidal proteins but the molecular details of their activity are not understood. As a 30 first step in the structural characterisation of these proteins we have analysed their secondary 31 structure and resolved the surface topology of a tetrameric complex of the Vip3Ag4 protein by 32 transmission electron microscopy. Sites sensitive to proteolysis by trypsin are identified and the 33 trypsin-cleaved protein appears to retain a similar structure as an octomeric complex comprising 34 four copies each of the ~65 kDa and ~21 kDa products of proteolysis. This processed form of the 35 toxin may represent the active toxin. The quality and monodispersity of the protein produced in 36 this study make Vip3Ag4 a candidate for more detailed structural analysis using cryo-electron 37 microscopy.

Nucleic acids symposium series 44(10), 4947 - 4956(2016). doi:10.1093/nar/gkw191, The IncP (Incompatibility group P) plasmids are important carriers in the spread of antibiotic resistance across Gram-negative bacteria. Gene expression in the IncP-1 plasmids is stringently controlled by a network of four global repressors, KorA, KorB, TrbA and KorC interacting cooperatively. Intriguingly, KorA and KorB can act as co-repressors at varying distances between their operators, even when they are moved to be on opposite sides of the DNA. KorA is a homodimer with the 101-amino acid subunits, folding into an N-terminal DNA-binding domain and a C-terminal dimerization domain. In this study, we have determined the structures of the free KorA repressor and two complexes each bound to a 20-bp palindromic DNA duplex containing its consensus operator sequence. Using a combination of X-ray crystallography, nuclear magnetic resonance spectroscopy, SAXS and molecular dynamics calculations, we show that the linker between the two domains is very flexible and the protein remains highly mobile in the presence of DNA. This flexibility allows the DNA-binding domains of the dimer to straddle the operator DNA on binding and is likely to be important in cooperative binding to KorB. Unexpectedly, the C-terminal domain of KorA is structurally similar to the dimerization domain of the tumour suppressor p53., Published by Oxford Univ. Press, Oxford

In this study we introduce the first step towards a statistical model for the reliability of fisheries data. We applied Benford's Law to catch data from the Atlantic Canadian lobster (Homarus americanus) fishery's lobster fishery areas (LFAs) 33 and 34 and compared our results to those using observations from the “grey zone” (a highly regulated lobster fishery shared by Canada and United States) and a fishery with a different regulatory regime (snow crab, Chionoecetes opilio). Non‐conformity with Benford's Law is often considered as an indicator of human manipulation of accounting data. We found that observations from the grey zone conformed to the distribution predicted by Benford's Law, whereas observations from snow crab and both lobster fishery areas did not conform.

Paradoxical embolus through a patent foramen ovale is a well-reported phenomenon. Clinical consequences include stroke, intestinal infarction, lower limb ischaemia, and even acute myocardial infarction (MI), via embolisation to the coronary arteries. We present a case of acute MI, cardiogenic shock, and cardiac arrest caused not by this mechanism, but by embolisation of thrombotic material to the aortic root with transient complete occlusion of the left main stem (LMS) coronary artery. During percutaneous coronary intervention to treat this occlusion the thrombus became lodged at the aortic bifurcation causing lower limb ischaemia. Despite successful treatment of this via bilateral groin exploration and thromboembolectomy the patient became increasingly acidotic and an abdominal and pelvic CT scan was performed. This revealed the source of the thrombus to be the patient’s congested and compressed pelvic veins which were the result of a large, previously undiagnosed ovarian malignancy with metastatic spread. Although very unusual we feel this case highlights an important differential in the diagnosis of anterolateral MI and images similar to those presented here are previously unreported in the literature.

3 pp. (2006)., Polarized $e^+$ and $e^-$ beams are foreseen for the future International Linear Collider (ILC) whose final basic de- sign considerations are currently under discussion. High precision physics requires the polarization of both beams to be known with a relative uncertainty of about 0.5% or bet- ter. Therefore all possible depolarizing effects that could operate between the polarized sources and the interaction regions have to be under full control.The ‘heLiCal’ collaboration aims to provide a full ‘cradle-to-grave’ analysis of all depolarizing effects at the ILC. This report gives a brief summary of ongoing work on the ILC spin-dynamics concentrating on recent results for depolarizing effects in the ILC damping rings, beam delivery system and beam-beam interactions. The effects during the beam-beam interactions have been evaluated for a range of ILC parameter sets.