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Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers.Significance:This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer.See related commentary by Letai, p. 290.This article is highlighted in the In This Issue feature, p. 275

Personalized medicine aims to match the right drug with the right patient by using specific features of the individual patient's tumor. However, current strategies of personalized therapy matching provide treatment opportunities for less than 10% of patients with cancer. A promising method may be drug profiling of patient biopsy specimens with single-cell resolution to directly quantify drug effects. We prospectively tested an image-based single-cell functional precision medicine (scFPM) approach to guide treatments in 143 patients with advanced aggressive hematologic cancers. Fifty-six patients (39%) were treated according to scFPM results. At a median follow-up of 23.9 months, 30 patients (54%) demonstrated a clinical benefit of more than 1.3-fold enhanced progression-free survival compared with their previous therapy. Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. We conclude that therapy matching by scFPM is clinically feasible and effective in advanced aggressive hematologic cancers. Significance: This is the first precision medicine trial using a functional assay to instruct n-of-one therapies in oncology. It illustrates that for patients lacking standard therapies, high-content assay-based scFPM can have a significant value in clinical therapy guidance based on functional dependencies of each patient's cancer. See related commentary by Letai, p. 290. This article is highlighted in the In This Issue feature, p. 275

We have designed and developed an experimental setup to measure the Seebeck coefficient of a variety of samples at cryogenic temperatures and under magnetic fields up to 7 T employing the physical property measurement system (PPMS). The measurement technique uses a low frequency ac thermal gradient generated by two thin film heaters in thermal contact with the sample. Heaters and temperature sensors are all fitted on a standard PPMS sample puck. The validity of this method is tested by measuring the thermoelectric power of several superconductors and thermoelectric samples. We have used this technique to measure the thermoelectric power of various topological insulator single crystals (Pb0.8Sn0.2Te, Bi2Te3, Bi2Se2.1Te0.9, and Sb2Te3). The developed hardware and software control is suitable for studying the thermoelectric power of small samples (length 2 mm) in a commercial cryomagnetic system (PPMS) and it allows for studying superconductor, semiconductor, thermoelectric, or topological insulator material in wide temperature (2–300 K) and magnetic field (0–7 T) ranges.

Um Sicherheit und Umweltvertraglichkeit von Strasen- bzw. Kraftfahrzeugen zu gewahrleisten, werden an die Gestaltung der Fahrzeuge technische Anforderungen gestellt. Es gibt Anforderungen durch den Gesetzgeber, die erfullt werden mussen, um ein Fahrzeug in den Verkehr bringen zu durfen. Daruber hinaus bestehen herstellerinterne Anforderungen an das Produkt, die uber das vom Gesetzgeber geforderte Mas hinausgehen, um den Kundenwunschen und der Firmenphilosophie zu genugen. Und als dritter Punkt stellen auch Verbraucherschutzorganisationen Kriterien auf, anhand derer sie die Eigenschaften der auf dem Markt befindlichen Fahrzeuge bewerten und die Fahrzeuge eingruppieren, was dann der Kundeninformation dient. Auch diese Anforderungen gehen uber die des Gesetzgebers hinaus.

Shubnikov-de Haas (SdH) oscillations in metallic Bi2Se2.1Te0.9 are studied in magnetic fields up to 35 Tesla. It is demonstrated that two characteristic frequencies determine the quantum oscillations of the conductivity. Angle dependent measurements and calculations of the Berry phase show that the two frequencies F1 and F2 describe oscillations from surface and bulk carriers, respectively. At low magnetic fields, only SdH oscillation from topological surface states can be detected whereas at high magnetic field the bulk oscillations dominate. The origin of the separation of bulk and surface SdH oscillations into different magnetic field ranges is revealed in the difference of the cyclotron masses mc. The bulk mc is nearly three times larger than the surface cyclotron mass resulting in a stronger attenuation of the bulk oscillation amplitude upon decreasing magnetic field. This makes it possible to detect and characterize the surface SdH oscillations in the low-field range and the bulk oscillations at high magnetic fields.

Hexagonal manganites belong to an exciting class of materials exhibiting strong interactions between a highly frustrated magnetic system, the ferroelectric polarization, and the lattice. The existence and mutual interaction of different magnetic ions (Mn and rare earth) results in complex magnetic phase diagrams and novel physical phenomena. A summary and discussion of the various properties, underlying physical mechanisms, the role of the rare earth ions, and the complex interactions in multiferroic hexagonal manganites are presented in this review.

We used single-crystal neutron diffraction to investigate the magnetic structures of the multiferroic ${\mathrm{GdMn}}_{2}{\mathrm{O}}_{5}$. The system undergoes a first-order incommensurate to commensurate magnetic transition below 33 K, accompanied by the appearance of electric polarization $P$. Upon cooling, $P$ increases smoothly while the magnetic order shows an abrupt enhancement in intensity below 20 K owing to the large increase of the rare-earth Gd moment. The contrasting temperature evolution of the magnetic order and polarization indicates the polarization is mainly driven by the exchange striction between the magnetic Mn ions. The incommensurate phase in the intermediate temperature range has a cycloidal modulation along the $c$ axis, with spin configuration projected in the $ab$ plane similar to the commensurate phase. The lack of observable bulk polarization suggests the exchange striction is not the dominant mechanism for the polarization in the incommensurate phase.

We have synthesized high-quality single crystals of SnxPb1-xTe and carried out detailed studies of the magnetotransport properties of one of the samples, Sn0.05Pb0.95Te. Longitudinal magnetoresistance increases almost linearly with increasing applied field (H) and reaches ∼310% atH= 13 T. At higher fields, both longitudinal and Hall resistance show clear Shubnikov de Haas oscillations. The oscillations are smooth and periodic, and there exists only one frequency,fα∼ 57 T. However, an additional frequency,fβ∼ 69 T, appears as the angle between the field direction and the normal to the sample surface (θ) is increased. Bothfαandfβexhibitθ-dependence;fαdecreases whereasfβincreases gradually with increasingθ. The presence of two frequencies in Sn0.05Pb0.95Te indicates that there exist two Fermi surface pockets (αandβpockets). We have constructed the Landau-level fan plot and determined the Berry phase (δ) for theαpocket to beδ∼ 0.1. Thisδvalue is very close to the expected value of 0 for a topologically trivial system.

The pressure effect on the ferroelectric (FE) properties of the multiferroic compounds GdMn2O5 and TmMn2O5 was studied up to 18.2 kbars. A new FE phase was observed at a higher temperature in GdMn2O5 above a critical pressure, $P_{c} \approx ~10$ kbars. Our results indicate that pressure decouples the Gd moment from Mn spin system and splits the FE phase. Thermal expansion measurements reveal a large increase of the $c$ -axis at the ambient-pressure FE transition. The pressure-induced contraction of the $c$ lattice parameter is considered to be the origin of the decoupling of both spin systems above $P_{c}$ . From the dielectric and FE properties of GdMn2O5, a pressure–temperature phase diagram can be derived. While a new phase was discovered for GdMn2O5, no significant change in polarization was observed for TmMn2O5 up to 16.6 kbars.

Using high-resolution inelastic neutron scattering, we examine the spin dynamics of ${\mathrm{Mn}}_{1\ensuremath{-}x}{\mathrm{Co}}_{x}{\mathrm{WO}}_{4}$ in the collinear AF1, the $ac\text{\ensuremath{-}}b$ spiral AF2, and the $ac$ cycloidal AF5 phases. The spin wave excitations are well described by a Heisenberg model with competing long-range exchange interactions $({J}_{i}$ up to 12th nearest neighbors) and the single-ion anisotropy $K$ induced by the spin-orbit interaction. While the exchange constants are relatively unchanged, the dominant effect of doping is to change the single-ion anisotropy from easy axis $(Kg0)$ in the collinear AF1 phase to easy plane $(Kl0)$ in the two multiferroic phases.

Raman scattering spectroscopy is used to monitor the transition of reduced niobium oxyfluoride ${\mathrm{Nb}}_{2}{\mathrm{O}}_{2}{\mathrm{F}}_{3}$ single crystals from their high-temperature monoclinic (I2/a) phase into the low-temperature triclinic ($P\overline{1}$) phase at ${T}_{c}\phantom{\rule{4pt}{0ex}}\ensuremath{\approx}90\phantom{\rule{4.pt}{0ex}}\text{K}$ due to charge disproportionation of (${\mathrm{Nb}\text{\ensuremath{-}}\mathrm{Nb})}^{7+}$ dimers and creation of crystallographically nonequivalent dimers with long and short Nb-Nb bonds. The group-theoretic analysis of lattice vibrations is performed, and the assignment of observed phonon lines to the specific lattice eigenmodes of the two phases is achieved based on a comparison with the results of density functional lattice dynamics calculations. Nb-Nb dimers are found to possess stretching vibrational frequencies as high as 382 ${\mathrm{cm}}^{\ensuremath{-}1}$. Strikingly, the kinetics of the monoclinic-to-triclinic structural transformation and the volume fraction of corresponding phases below ${T}_{c}$ are shown to strongly depend upon the sample cooling rate. Fast cooling results in a ``freezing'' of the high-temperature monoclinic phase and allows us to observe a spin-ordered state below ${\mathrm{T}}_{N}\ensuremath{\approx}$ 49 K.

A new niobium oxyfluoride, Nb2O2F3, synthesized through the reaction of Nb, SnO, and SnF2 in Sn flux, within welded Nb containers, crystallizes in a monoclinic structure (space group: I2/a; a = 5.7048(1)Å, b = 5.1610(1)Å, c = 12.2285(2)Å, β = 95.751(1)°). It features [Nb2X10] units (X = O, F), with short (2.5739(1) Å) Nb-Nb bonds, that are linked through shared O/F vertices to form a 3D structure configurationally isotypic to ζ-Nb2O5. Nb2O2F3 undergoes a structural transition at ∼90 K to a triclinic structure (space group: P1̅; a = 5.1791(5)Å, b = 5.7043(6)Å, c = 6.8911(7)Å, α = 108.669(3)°, β = 109.922(2)°, γ = 90.332(3)°). The transition is described as a disproportionation or charge ordering of [Nb2](7+) dimers: (2[Nb2](7+) → [Nb2](6+) + [Nb2](8+)), resulting in doubly (2.5000(9) Å) and singly bonded (2.6560(9) Å) Nb2 dimers. The structural transition is accompanied by an unusual field-independent "spin-gap-like" magnetic transition.

Reported results for thyroid nodule fine-needle aspiration (FNA) cytology mainly originate from tertiary centers. However, thyroid nodule FNA cytology is mainly performed in primary care settings for which the distribution of FNA Bethesda categories and their respective malignancy rates are largely unknown. Therefore, this study investigated FNA cytology malignancy rates of a large primary care setting to determine to what extent current evidence-based strategies for the malignancy risk stratification of thyroid nodules are applied and applicable in such primary care settings.In a primary care setting, 9460 FNAs of thyroid nodules were retrospectively analyzed from 8380 patients evaluated by one cytologist (I.R.) during a period of two years. The 8380 FNA cytologies were performed by 64 physicians in different private practices throughout Germany in primary care settings.The cytopathologic results were classified according to the Bethesda System as non-diagnostic in 19%, cyst/cystic nodule in 21%, benign (including thyroiditis) in 48%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) in 6%, follicular neoplasms/suspicious for follicular neoplasm (FN/SFN) in 4%, suspicious for malignancy (SFM) in 1%, and malignant in 1%. The proportion of patients proceeding to surgery or with a follow-up of at least one year and the observed risks of malignancy were 22%/8% for AUS/FLUS, 69%/17% for FN/SFN, 78%/86% for SFM, and 71%/98% for malignant. For 112 cytologically suspicious and malignant FNAs, there were 102 true positives and 10 false positives, considering histology as gold standard.At variance with other data mostly originating from tertiary centers, these data demonstrate low percentages for malignant, SFM, FN/SFN, and AUS/FLUS, and high percentages for cysts/cystic nodules in this primary care setting in Germany. The risks of malignancy for malignant, SFM, AUS/FLUS, and FN/SFN FNA cytologies are according to Bethesda recommendations.

We have investigated the weak antilocalization (WAL) effect in the p-type Bi$_2$Se$_{2.1}$Te$_{0.9}$ topological system. The magnetoconductance shows a cusp-like feature at low magnetic fields, indicating the presence of the WAL effect. The WAL curves measured at different tilt angles merge together when they are plotted as a function of the normal field components, showing that surface states dominate the magnetoconductance in the Bi$_2$Se$_{2.1}$Te$_{0.9}$ crystal. We have calculated magnetoconductance per conduction channel and applied the Hikami-Larkin-Nagaoka formula to determine the physical parameters that characterize the WAL effect. The number of conduction channels and the phase coherence length do not change with temperature up to T=5 K. In addition, the sample shows a large positive magnetoresistance that reaches 1900% under a magnetic field of 35 T at T=0.33K with no sign of saturation. The magnetoresistance value decreases with both increasing temperature and tilt angle of the sample surface with respect to the magnetic field. The large magnetoresistance of topological insulators can be utilized in future technology such as sensors and memory devices., 5 pages, 4 figures