Treatment of advanced seminoma with cyclophosphamide, vincristine and carboplatin on an outpatient basis.

This study describes the efficacy and toxicity of a combination regimen consisting of cyclophosphamide, vincristine (oncovin) and carboplatin (COC) for advanced seminoma on an outpatient basis. Twenty-seven patients (mean age 43 years, range 28-63 years) were classified as stage IIC (n = 5), stage IID (n = 12), stage III (n = 9) or stage IV (n = 1). Six had been treated with prior radiotherapy; elevated beta-HCG and elevated LDH serum levels were observed in 15 and 25 patients respectively. Patients were treated with four cycles of 750 mg m-2 cyclophosphamide intravenously (i.v.), 1.4 mg m-2 vincristine i.v. (maximum 2 mg) and carboplatin adjusted to creatinine clearance. Cycles were given at 3 week intervals. The median dose of carboplatin administered was 400 mg m-2 (range 300-450 mg m-2). Six patients [22%; 95% confidence interval (CI), 6-38%] achieved a complete response (CR), 19 (70%; 95% CI, 51-88%) a partial response and two (8%; 95% CI, 0 18%) showed only a response in tumour markers but not a reduction of retroperitoneal mass (NR). Post-chemotherapeutic masses were not removed surgically or irradiated. After a median follow-up of 26 months (range 5-69 months), two patients have died, one from cardiac arrest 2 years after achieving CR, the other with relapsed seminoma 5 months after therapy. None of the other patients relapsed. Main toxicity was haematological, with 22 patients (81%) experiencing thrombocytopenia WHO grade III/IV and 27 (100%) leucocytopenia WHO grade III/IV, requiring dose reduction in five patients. Seven patients experienced granulocytopenic fever. Non-haematological toxicity was rare. Peripheral neuropathy grade I was observed in four patients and grade III in one. Haemorrhagic cystitis occurred once. In conclusion, despite considerable haematological toxicity, COC is feasible on an outpatient basis, even after prior radiotherapy, and is an effective regimen for advanced seminoma with only 1/27 treatment failures after a median follow-up of 26 months

Calculated corrections to superallowed Fermi beta decay: New evaluation of the nuclear-structure-dependent terms

The measured $ft$-values for superallowed $0^{+} \to 0^{+}$ nuclear $\beta$-decay can be used to obtain the value of the vector coupling constant and thus to test the unitarity of the Cabibbo-Kobayashi-Maskawa matrix. An essential requirement for this test is accurate calculations for the radiative and isospin symmetry-breaking corrections that must be applied to the experimental data. We present a new and consistent set of calculations for the nuclear-structure-dependent components of these corrections. These new results do not alter the current status of the unitarity test -- it still fails by more than two standard deviations -- but they provide calculated corrections for eleven new superallowed transitions that are likely to become accessible to precise measurements in the future. The reliability of all calculated corrections is explored and an experimental method indicated by which the structure-dependent corrections can be tested and, if necessary, improved.Comment: Revtex4, one figur

Subharmonic Shapiro steps and assisted tunneling in superconducting point contacts

We analyze the current in a superconducting point contact of arbitrary transmission in the presence of a microwave radiation. The interplay between the ac Josephson current and the microwave signal gives rise to Shapiro steps at voltages V = (m/n) \hbar \omega_r/2e, where n,m are integer numbers and \omega_r is the radiation frequency. The subharmonic steps (n different from 1) are a consequence of the ocurrence of multiple Andreev reflections (MAR) and provide an unambiguous signature of the peculiar ac Josephson effect at high transmission. Moreover, the dc current exhibits a rich subgap structure due to photon-assisted MARs.Comment: Revtex, 4 pages, 4 figure

Isospin-mixing corrections for fp-shell Fermi transitions

Isospin-mixing corrections for superallowed Fermi transitions in {\it fp}-shell nuclei are computed within the framework of the shell model. The study includes three nuclei that are part of the set of nine accurately measured transitions as well as five cases that are expected to be measured in the future at radioactive-beam facilities. We also include some new calculations for $^{10}$C. With the isospin-mixing corrections applied to the nine accurately measured $ft$ values, the conserved-vector-current hypothesis and the unitarity condition of the Cabbibo-Kobayashi-Maskawa (CKM) matrix are tested.Comment: 13 pages plus five tables. revtex macro

Resistively-shunted superconducting quantum point contacts

We have studied the Josephson dynamics of resistively-shunted ballistic superconducting quantum point contacts at finite temperatures and arbitrary number of conducting modes. Compared to the classical Josephson dynamics of tunnel junctions, dynamics of quantum point contacts exhibits several new features associated with temporal fluctuations of the Josephson potential caused by fluctuations in the occupation of the current-carrying Andreev levels.Comment: 5 pages, RevTex, 3 postscript figures include

Molecular analysis of enrichment cultures of ammonia oxidizers from the Salar de Huasco, a high altitude saline wetland in northern Chile

We analyzed enrichment cultures of ammonia-oxidizing bacteria (AOB) collected from different areas of Salar de Huasco, a high altitude, saline, pH-neutral water body in the Chilean Altiplano. Samples were inoculated into mineral media with 10 mM NH4+ at five different salt concentrations (10, 200, 400, 800 and 1,400 mM NaCl). Low diversity (up to three phylotypes per enrichment) of beta-AOB was detected using 16S rDNA and amoA clone libraries. Growth of beta-AOB was only recorded in a few enrichment cultures and varied according to site or media salinity. In total, five 16S rDNA and amoA phylotypes were found which were related to Nitrosomonas europaea/Nitrosococcus mobilis, N. marina and N. communis clusters. Phylotype 1-16S was 97% similar with N. halophila, previously isolated from Mongolian soda lakes, and phylotypes from amoA sequences were similar with yet uncultured beta-AOB from different biofilms. Sequences related to N. halophila were frequently found at all salinities. Neither gamma-AOB nor ammonia-oxidizing Archaea were recorded in these enrichment cultures

Cloning and functional characterization of a fructan 1-exohydrolase (1-FEH) in edible burdock (Arctium lappa L.)

<p>Abstract</p> <p>Background</p> <p>We have previously reported on the variation of total fructooligosaccharides (FOS), total inulooligosaccharides (IOS) and inulin in the roots of burdock stored at different temperatures. During storage at 0°C, an increase of FOS as a result of the hydrolysis of inulin was observed. Moreover, we suggested that an increase of IOS would likely be due to the synthesis of the IOS by fructosyltransfer from 1-kestose to accumulated fructose and elongated fructose oligomers which can act as acceptors for fructan:fructan 1-fructosyltransferase (1-FFT). However, enzymes such as inulinase or fructan 1-exohydorolase (1-FEH) involved in inulin degradation in burdock roots are still not known. Here, we report the isolation and functional analysis of a gene encoding burdock 1-FEH.</p> <p>Results</p> <p>A cDNA, named <it>aleh1</it>, was obtained by the RACE method following PCR with degenerate primers designed based on amino-acid sequences of FEHs from other plants. The <it>aleh1 </it>encoded a polypeptide of 581 amino acids. The relative molecular mass and isoelectric point (<it>pI</it>) of the deduced polypeptide were calculated to be 65,666 and 4.86. A recombinant protein of <it>aleh1 </it>was produced in <it>Pichia pastoris</it>, and was purified by ion exchange chromatography with DEAE-Sepharose CL-6B, hydrophobic chromatography with Toyopearl HW55S and gel filtration chromatography with Toyopearl HW55S. Purified recombinant protein showed hydrolyzing activity against β-2, 1 type fructans such as 1-kestose, nystose, fructosylnystose and inulin. On the other hand, sucrose, neokestose, 6-kestose and high DP levan were poor substrates.</p> <p>The purified recombinant protein released fructose from sugars extracted from burdock roots. These results indicated that <it>aleh1 </it>encoded 1-FEH.</p

Molecule-by-Molecule Writing Using a Focused Electron Beam

The resolution of lithography techniques needs to be extended beyond their current limits to continue the trend of miniaturization and enable new applications. But what is the ultimate spatial resolution? It is known that single atoms can be imaged with a highly focused electron beam. Can single atoms also be written with an electron beam? We verify this with focused electron-beam-induced deposition (FEBID), a direct-write technique that has the current record for the smallest feature written by (electron) optical lithography. We show that the deposition of an organometallic precursor on graphene can be followed molecule-by-molecule with FEBID. The results show that mechanisms that are inherent to the process inhibit a further increase in control over the process. Hence, our results present the resolution limit of (electron) optical lithography techniques. The writing of isolated, subnanometer features with nanometer precision can be used, for instance, for the local modification of graphene and for catalysis.</p

Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction

OBJECTIVE: Recent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality. METHODS: From 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients. RESULTS: Of 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75–0.94, p = 0.002) for mortality and 0.85 (0.78–0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years. CONCLUSIONS: This study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF. SUPPLEMENTARY INFORMATION: The online version of this article (10.1007/s12471-021-01591-6) contains supplementary material, which is available to authorized users