Is large-scale rapid CoV-2 testing a substitute for lockdowns?

BACKGROUND: Various forms of contact restrictions have been adopted in response to the Covid-19 pandemic. Around February 2021, rapid testing appeared as a new policy instrument. Some claim it may serve as a substitute for contact restrictions. We study the strength of this argument by evaluating the effects of a unique policy experiment: In March and April 2021, the city of Tübingen set up a testing scheme while relaxing contact restrictions. METHODS: We compare case rates in Tübingen county to an appropriately identified control unit. We employ the synthetic control method. We base interpretations of our findings on an extended SEIR model. FINDINGS: The experiment led to an increase in the reported case rate. This increase is robust across alternative statistical specifications. This is also due to more testing leading initially to more reported cases. An epidemiological model that corrects for 'more cases due to more testing' and 'reduced testing and reporting during the Easter holiday' confirms that the overall effect of the experiment led to more infections. INTERPRETATION: The number of rapid tests were not sufficiently high in this experiment to compensate for more contacts and thereby infections caused by relaxing contact restrictions.

Quantitative analysis of left ventricular strain using cardiac computed tomography.

OBJECTIVES: To investigate whether cardiac computed tomography (CCT) can determine left ventricular (LV) radial, circumferential and longitudinal myocardial deformation in comparison to two-dimensional echocardiography in patients with congestive heart failure. BACKGROUND: Echocardiography allows for accurate assessment of strain with high temporal resolution. A reduced strain is associated with a poor prognosis in cardiomyopathies. However, strain imaging is limited in patients with poor echogenic windows, so that, in selected cases, tomographic imaging techniques may be preferable for the evaluation of myocardial deformation. METHODS: Consecutive patients (n=27) with congestive heart failure who underwent a clinically indicated ECG-gated contrast-enhanced 64-slice dual-source CCT for the evaluation of the cardiac veins prior to cardiac resynchronization therapy (CRT) were included. All patients underwent additional echocardiography. LV radial, circumferential and longitudinal strain and strain rates were analyzed in identical midventricular short axis, 4-, 2- and 3-chamber views for both modalities using the same prototype software algorithm (feature tracking). Time for analysis was assessed for both modalities. RESULTS: Close correlations were observed for both techniques regarding global strain (r=0.93, r=0.87 and r=0.84 for radial, circumferential and longitudinal strain, respectively, p<0.001 for all). Similar trends were observed for regional radial, longitudinal and circumferential strain (r=0.88, r=0.84 and r=0.94, respectively, p<0.001 for all). The number of non-diagnostic myocardial segments was significantly higher with echocardiography than with CCT (9.6% versus 1.9%, p<0.001). In addition, the required time for complete quantitative strain analysis was significantly shorter for CCT compared to echocardiography (877±119 s per patient versus 1105±258 s per patient, p<0.001). CONCLUSION: Quantitative assessment of LV strain is feasible using CCT. This technique may represent a valuable alternative for the assessment of myocardial deformation in selected patients with poor echogenic windows and general contraindications for magnetic resonance imaging.

Amine-borane mediated metal-free hydrogen activation and catalytic hydrogenation.

The use of frustrated Lewis pairs (FLPs) as hydrogenation catalysts is attracting increasing attention as one of the most modern and rapidly growing areas of organic chemistry, with many research groups around the world working on this subject. Since the pioneering studies of the groups of Stephan and Piers on the Lewis acid-base pairs, which do not react irreversibly with each other and act as a trap for small molecules, numerous FLPs for hydrogen activation have been reported. Among others, intra- and intermolecular systems based on phosphines, organic carbenes, amines as Lewis bases, and boranes or alanes as Lewis acids were studied. This review presents a progression from the first observation of the facile heterolytical cleavage of hydrogen gas by amines and B(C6F5)3 to highly active non-metal catalysts for both enantioselective and racemic hydrogenation of unsaturated nitrogen-containing compounds and also internal alkynes.

Quantitative analysis of left ventricular dyssynchrony using cardiac computed tomography versus three-dimensional echocardiography.

OBJECTIVES: We investigated whether cardiac computed tomography (CCT) can determine intraventricular dyssynchrony in comparison to real-time three-dimensional echocardiography (RT3DE) in patients who are considered for cardiac resynchronisation therapy (CRT). METHODS: 35 patients considered for CRT were examined. Left ventricular (LV) dyssynchrony was quantified by calculating the standard deviation index (SDI) of 17 myocardial LV segments by RT3DE and ECG-gated contrast-enhanced 64-slice dual-source CCT. For both analyses the same software algorithm (4D LV-Analysis) was used. RESULTS: Close correlations were observed for end-systolic volume, end-diastolic volume and LV ejection fraction between the two techniques (r = 0.94, r = 0.92 and r = 0.95, respectively, P < 0.001 for all). For the global dyssynchrony index SDI, a high correlation was found between RT3DE and CCT (r = 0.84, P < 0.001), which further increased after exclusion of segments with poor image quality by echocardiography (r = 0.90, P < 0.001). The required time for quantitative analysis was significantly shorter (162 ± 22 s vs. 608 ± 112 s per patient, P < 0.001) and reproducibility was significantly higher for CCT compared with RT3DE (interobserver variability of 4.5 ± 3.1% vs. 7.9 ± 6.1%, P < 0.05). CONCLUSION: Quantitative assessment of LV dyssynchrony is feasible by CCT. Owing to its higher reproducibility and faster analysis time compared with RT3DE, this technique may represent a valuable alternative for dyssynchrony assessment. KEY POINTS: • Quantitative assessment of left ventricular dyssynchrony is feasible by cardiac computed tomography (CCT). • This technique has been compared with real-time three-dimensional echocardiography (RT3DE). • Reproducibility is significantly higher for CCT compared with RT3DE. • Time spent for analysis is significantly shorter for CCT. • Computed tomography may represent a valuable alternative to ultrasound for dyssynchrony assessment.

Molecular hydrogen tweezers: structure and mechanisms by neutron diffraction, NMR, and deuterium labeling studies in solid and solution.

The mechanism of reversible hydrogen activation by ansa-aminoboranes, 1-N-TMPH-CH(2)-2-[HB(C(6)F(5))(2)]C(6)H(4) (NHHB), was studied by neutron diffraction and thermogravimetric mass-spectroscopic experiments in the solid state as well as with NMR and FT-IR spectroscopy in solution. The structure of the ansa-ammonium borate NHHB was determined by neutron scattering, revealing a short N-H···H-B dihydrogen bond of 1.67 Å. Moreover, this intramolecular H-H distance was determined in solution to be also 1.6-1.8 Å by (1)H NMR spectroscopic T(1) relaxation and 1D NOE measurements. The X-ray B-H and N-H distances deviated from the neutron and the calculated values. The dynamic nature of the molecular tweezers in solution was additionally studied by multinuclear and variable-temperature NMR spectroscopy. We synthesized stable, individual isotopic isomers NDDB, NHDB, and NDHB. NMR measurements revealed a primary isotope effect in the chemical shift difference (p)Δ(1)H(D) = δ(NH) - δ(ND) (0.56 ppm), and hence supported dihydrogen bonding. The NMR studies gave strong evidence that the structure of NHHB in solution is similar to that in the solid state. This is corroborated by IR studies providing clear evidence for the dynamic nature of the intramolecular dihydrogen bonding at room temperature. Interestingly, no kinetic isotope effect was detected for the activation of deuterium hydride by the ansa-aminoborane NB. Theoretical calculations attribute this to an "early transition state". Moreover, 2D NOESY NMR measurements support fast intermolecular proton exchange in aprotic CD(2)Cl(2) and C(6)D(6).

Synthesis and biological activity of splitomicin analogs targeted at human NAD(+)-dependent histone deacetylases (sirtuins).

Small molecules interfering with posttranslational modification of histones are of interest as tools to study epigenetic regulation of gene transcription. Specifically, drugs that interfere with histone deacetylation could be useful to induce differentiation, growth arrest as well as apoptotic cell death in tumor cells. One class of histone deacetylases is known as sirtuins some of which (Saccharomyces cerevisiae Sir2) are for example inhibited by the lactone splitomicin leading to telomeric silencing in yeast. However, splitomicin is only a micromolar inhibitor of yeast Sir2 and does not inhibit human subtypes and the lactone is prone to hydrolytic ring opening. In preliminary SAR-studies, splitomicin analogs lacking this hydrolytically labile ring were described as inactive while the naphthalene moiety could successfully be replaced by smaller aromatic rings in a fragment-like dihydrocoumarin. Here we report the synthesis and biological activity of a series of hydrolytically stable analogs with activity against human SIRT1 and 2. These comparatively small compounds characterized by high ligand efficiency are used as a starting point toward the development of specific inhibitors of histone deacetylases from the class of sirtuins.

Image quality and radiation dose in 256-slice cardiac computed tomography: comparison of prospective versus retrospective image acquisition protocols.

PURPOSE: To assess coronary artery image quality and patient radiation exposure in patients who underwent clinically indicated 256-slice CTA. METHODS: Consecutive patients (n=193) underwent 256-slice CTA, using (1) retrospective gating without radiation dose modulation, (2) retrospective gating with radiation dose modulation and (3) prospective gating. Image quality was determined by consensus of two experienced observers using a 5-grade scale. The effective dose was calculated. RESULTS: In all patients, CTA was performed without adverse events. Retrospective CTA was assessed in 39 patients with and 39 without dose modulation, while 115 patients underwent prospective CTA. Heart rate was related to image quality with all protocols (r=0.46, p<0.001). Up to a heart rate of 75 bpm no significant difference in overall image quality was observed for all three protocols, while no significant differences could be observed between retrospective CTA with and without dose modulation for any segments or heart rates. Prospective and retrospective CTA with dose modulation showed radiation savings of ∼75 % and ∼30 %, respectively compared to retrospective CTA without dose modulation (p<0.001). CONCLUSIONS: In patients with heart rates up to 75 bpm prospective CTA should be the first choice acquisition protocol. For heart rates >75 bpm, retrospective CTA with dose modulation should be considered.

Frustrated Lewis pairs: reactivities of TMS protected amines and phosphines in the presence of B(C(6)F(5))(3).

TMS protected amines in combination with B(C(6)F(5))(3) were found to activate H(2) and this is followed by a cleavage of the N-Si bond and the generation of TMSH. A TMS protected phosphine on the other hand reacts rapidly with B(C(6)F(5))(3) to give the known compound tBu(2)P(C(6)F(4))B(C(6)F(5))(2) by a facile and efficient route.

Molecular tweezers for hydrogen: synthesis, characterization, and reactivity.

The first ansa-aminoborane N-TMPN-CH2C6H4B(C6F5)2 (where TMPNH is 2,2,6,6-tetramethylpiperidinyl) which is able to reversibly activate H2 through an intramolecular mechanism is synthesized. This new substance makes use of the concept of molecular tweezers where the active N and B centers are located close to each other so that one H2 molecule can fit in this void and be activated. Because of the fixed geometry of this ansa-ammonium-borate it forms a short N-H...H-B dihydrogen bond of 1.78 A as determined by X-ray analysis. Therefore, the bound hydrogen can be released above 100 degrees C. In addition, the short H...H contact and the N-H...H (154 degrees) and B-H...H (125 degrees) angles show that the dihydrogen interaction in N-TMPNH-CH2C6H4BH(C6F5)2 is partially covalent in nature. As a basis for discussing the mechanism, quantum chemical calculations are performed and it is found that the energy needed for splitting H2 can arise from the Coulomb attraction between the resulting ionic fragments, or "Coulomb pays for Heitler-London". The air- and moisture-stable N-TMPNH-CH2C6H4BH(C6F5)2 is employed in the catalytic reduction of nonsterically demanding imines and enamines under mild conditions (110 degrees C and 2 atm of H2) to give the corresponding amines in high yields.