Evaluation of the impact of buffered peptone water composition on the discrimination between Salmonella enterica and Escherichia coli by Raman spectroscopy.

The detection of Salmonella spp. in food samples is regulated by the ISO 6579:2002 standard, which requires that precise procedures are followed to ensure the reliability of the detection process. This standard requires buffered peptone water as a rich medium for the enrichment of bacteria. However, the effects of different brands of buffered peptone water on the identification of microorganisms by Raman spectroscopy are unknown. In this regard, our study evaluated the discrimination between two bacterial species, Salmonella enterica and Escherichia coli, inoculated and analyzed with six of the most commonly used buffered peptone water brands. The results showed that bacterial cells behaved differently according to the brand used in terms of biomass production and the spectral fingerprint. The identification accuracy of the analyzed strains was between 85% and 100% depending on the given brand. Several batches of two brands were studied to evaluate the classification rates between the analyzed bacterial species. The chemical analysis performed on these brands showed that the nutrient content was slightly different and probably explained the observed effects. On the basis of these results, Raman spectroscopy operators are encouraged to select an adequate culture medium and continue its use throughout the identification process to guarantee optimal recognition of the microorganism of interest.

Achieving orphan designation for placental insufficiency: annual incidence estimations in Europe.

OBJECTIVE: To determine whether a novel therapy for placental insufficiency could achieve orphan drug status by estimating the annual incidence of placental insufficiency, defined as an estimated fetal weight below the 10th centile in the presence of abnormal umbilical artery Doppler velocimetry, per 10 000 European Union (EU) population as part of an application for European Medicines Agency (EMA) orphan designation. DESIGN: Incidence estimation based on literature review and published national and EU statistics. SETTING AND POPULATION: European Union. METHODS: Data were drawn from published literature, including national and international guidelines, international consensus statements, cohort studies and randomised controlled trials, and published national and EU statistics, including birth rates and stillbirth rates. Rare disease databases were also searched. RESULTS: The proportion of affected pregnancies was estimated as 3.17% (95% CI 2.93-3.43%), using a weighted average of the results from two cohort studies. Using birth rates from 2012 and adjusting for a pregnancy loss rate of 1/100 gave an estimated annual incidence of 3.33 per 10 000 EU population (95% CI 3.07-3.60 per 10 000 EU population). This fell below the EMA threshold of 5 per 10 000 EU population. CONCLUSIONS: Maternal vascular endothelial growth factor gene therapy for placental insufficiency was granted EMA orphan status in 2015 after we demonstrated that it is a rare, life-threatening or chronically debilitating and currently untreatable disease. Developers of other potential obstetric therapies should consider applying for orphan designation, which provides financial and regulatory benefits. TWEETABLE ABSTRACT: Placental insufficiency meets the European Medicines Agency requirements for orphan disease designation.

The humanistic burden associated with caring for patients with advanced non-small cell lung cancer (NSCLC) in three European countries-a real-world survey of caregivers.

PURPOSE: This study evaluated the humanistic burden on caregivers of patients with advanced non-small cell lung cancer (aNSCLC) as the disease progresses. METHODS: Data were drawn from a cross-sectional study of patients with aNSCLC and their caregivers conducted in France, Germany, and Italy between 2015 and 2016. Data were collected by medical chart review and patient and caregiver questionnaires. The EuroQol five-dimension three-level (EQ-5D-3L) was used to evaluate patient and caregiver health status. Caregivers also completed the Work Productivity and Activity Impairment (WPAI) questionnaire and Zarit Burden Interview (ZBI). RESULTS: The population for the analysis consisted of 427 caregivers (mean age 53.5 years; 72.6% female; 54.9% spouse; 36.2% in full-time employment) and 427 matched patients (mean age 66.2 years; 68.6% male). Most (69.5%) patients were receiving first-line therapy for advanced disease. Patients' caregivers provided a mean of 29.5 h of support per week. Significant differences in EQ-5D-3L scores were observed between caregivers of patients receiving first and later lines of therapy in France (0.87 vs. 0.78; p = 0.0055). Among employed caregivers, overall work impairment was considerable and ranged from 21.1% in Germany to 30.4% in France and 29.7% in Italy. Caregivers of patients receiving later lines of therapy in France rated their own health status as significantly worse than did those caring for patients receiving first-line therapy (82.7 vs. 72.9; p = 0.0039). CONCLUSIONS: Informal caregivers provided the majority of support for patients with advanced NSCLC and their caregiving activities impose a significant humanistic burden.

Colossal Terahertz Magnetoresistance at Room Temperature in Epitaxial La0.7Sr0.3MnO3 Nanocomposites and Single-Phase Thin Films.

Colossal magnetoresistance (CMR) is demonstrated at terahertz (THz) frequencies by using terahertz time-domain magnetospectroscopy to examine vertically aligned nanocomposites (VANs) and planar thin films of La0.7Sr0.3MnO3. At the Curie temperature (room temperature), the THz conductivity of the VAN was dramatically enhanced by over 2 orders of magnitude under the application of a magnetic field with a non-Drude THz conductivity that increased with frequency. The direct current (dc) CMR of the VAN is controlled by extrinsic magnetotransport mechanisms such as spin-polarized tunneling between nanograins. In contrast, we find that THz CMR is dominated by intrinsic, intragrain transport: the mean free path was smaller than the nanocolumn size, and the planar thin-film exhibited similar THz CMR to the VAN. Surprisingly, the observed colossal THz magnetoresistance suggests that the magnetoresistance can be large for alternating current motion on nanometer length scales, even when the magnetoresistance is negligible on the macroscopic length scales probed by dc transport. This suggests that colossal magnetoresistance at THz frequencies may find use in nanoelectronics and in THz optical components controlled by magnetic fields. The VAN can be scaled in thickness while retaining a high structural quality and offers a larger THz CMR at room temperature than the planar film.

Impact of rare variants in ARHGAP29 to the etiology of oral clefts: role of loss-of-function vs missense variants.

Non-syndromic cleft lip with or without cleft palate (NSCL/P) is a prevalent, complex congenital malformation. Genome-wide association studies (GWAS) on NSCL/P have consistently identified association for the 1p22 region, in which ARHGAP29 has emerged as the main candidate gene. ARHGAP29 re-sequencing studies in NSCL/P patients have identified rare variants; however, their clinical impact is still unclear. In this study we identified 10 rare variants in ARHGAP29, including five missense, one in-frame deletion, and four loss-of-function (LoF) variants, in a cohort of 188 familial NSCL/P cases. A significant mutational burden was found for LoF (Sequence Kernel Association Test, p = 0.0005) but not for missense variants in ARHGAP29, suggesting that only LoF variants contribute to the etiology of NSCL/P. Penetrance was estimated as 59%, indicating that heterozygous LoF variants in ARHGAP29 confer a moderate risk to NSCL/P. The GWAS hits in IRF6 (rs642961) and 1p22 (rs560426 and rs4147811) do not seem to contribute to the penetrance of the phenotype, based on co-segregation analysis. Our data show that rare variants leading to haploinsufficiency of ARHGAP29 represent an important etiological clefting mechanism, and genetic testing for this gene might be taken into consideration in genetic counseling of familial cases.

Fluctuations and All-In-All-Out Ordering in Dipole-Octupole Nd(2)Zr(2)O(7).

By means of neutron scattering and magnetization measurements down to 90 mK, we determine the magnetic ground state of the spin-ice candidate Nd(2)Zr(2)O(7). We show that, despite ferromagnetic interactions, Nd(2)Zr(2)O(7) undergoes a transition around 285 mK towards an all-in-all-out antiferromagnetic state, with a strongly reduced ordered magnetic moment. We establish the (H,T) phase diagram in the three directions of the applied field and reveal a metamagnetic transition around 0.1 T, associated with an unexpected shape of the magnetization curves. We propose that this behavior results from the peculiar nature of the Nd^{3+} doublet, a dipolar-octupolar doublet, different from the standard Kramers doublet studied to date, thus revealing the importance of multipolar correlations in the properties of pyrochlore oxides.

Unconventional Superconductivity in La(7)Ir(3) Revealed by Muon Spin Relaxation: Introducing a New Family of Noncentrosymmetric Superconductor That Breaks Time-Reversal Symmetry.

The superconductivity of the noncentrosymmetric compound La(7)Ir(3) is investigated using muon spin rotation and relaxation. Zero-field measurements reveal the presence of spontaneous static or quasistatic magnetic fields below the superconducting transition temperature T(c)=2.25 K-a clear indication that the superconducting state breaks time-reversal symmetry. Furthermore, transverse-field rotation measurements suggest that the superconducting gap is isotropic and that the pairing symmetry of the superconducting electrons is predominantly s wave with an enhanced binding strength. The results indicate that the superconductivity in La(7)Ir(3) may be unconventional and paves the way for further studies of this family of materials.

Detection of time-reversal symmetry breaking in the noncentrosymmetric superconductor Re6Zr using muon-spin spectroscopy.

We have investigated the superconducting state of the noncentrosymmetric compound Re6Zr using magnetization, heat capacity, and muon-spin relaxation or rotation (µSR) measurements. Re6Zr has a superconducting transition temperature, Tc=6.75±0.05 K. Transverse-field µSR experiments, used to probe the superfluid density, suggest an s-wave character for the superconducting gap. However, zero and longitudinal-field µSR data reveal the presence of spontaneous static magnetic fields below Tc indicating that time-reversal symmetry is broken in the superconducting state and an unconventional pairing mechanism. An analysis of the pairing symmetries identifies the ground states compatible with time-reversal symmetry breaking.

Osteopathia striata congenita with cranial sclerosis and intellectual disability due to contiguous gene deletions involving the WTX locus.

Osteopathia striata congenita with cranial sclerosis (OSCS) is a skeletal dysplasia caused by germline deletions of or truncating point mutations in the X-linked gene WTX (FAM123B, AMER1). Females present with longitudinal striations of sclerotic bone along the long axis of long bones and cranial sclerosis, with a high prevalence of cleft palate and hearing loss. Intellectual disability or neurodevelopmental delay is not observed in females with point mutations in WTX leading to OSCS. One female has been described with a deletion spanning multiple neighbouring genes suggesting that deletion of some neighbouring loci may result in abnormal neurodevelopment. In this cohort of 13 females with OSCS resulting from deletions of WTX, a relationship is observed where deletion of ARHGEF9 and/or MTMR8 in conjunction with WTX results in an additional neurodevelopmental phenotype whereas deletion of ASB12 along with WTX is associated with a good neurodevelopmental prognosis.

X-linked CHARGE-like Abruzzo-Erickson syndrome and classic cleft palate with ankyloglossia result from TBX22 splicing mutations.

X-linked cleft palate (CPX) is caused by mutations in the gene encoding the TBX22 transcription factor and is known to exhibit phenotypic variability, usually involving either a complete, partial or submucous cleft palate, with or without ankyloglossia. This study hypothesized a possible involvement of TBX22 in a family with X-linked, CHARGE-like Abruzzo-Erickson syndrome, of unknown etiology. The phenotype extends to additional features including sensorineural deafness and coloboma, which are suggested by the Tbx22 developmental expression pattern but not previously associated in CPX patients. A novel TBX22 splice acceptor mutation (c.593-5T>A) was identified that tracked with the phenotype in this family. A novel splice donor variant (c.767+5G>A) and a known canonical splice donor mutation (c.767+1G>A) affecting the same exon were identified in patients with classic CPX phenotypes and were comparatively analyzed using both in silico and in vitro splicing studies. All three variants were predicted to abolish normal mRNA splicing and an in vitro assay indicated that use of alternative splice sites was a likely outcome. Collectively, the data showed the functional effect of several novel intronic splice site variants but most importantly confirms that TBX22 is the gene underlying Abruzzo-Erickson syndrome, expanding the phenotypic spectrum of TBX22 mutations.

Oral vs intravenous paracetamol for lower third molar extractions under general anaesthesia: is oral administration inferior?

BACKGROUND: Paracetamol formulations provide effective analgesia after surgery [Duggan ST, Scott LJ. Intravenous paracetamol (acetominophen). Drugs 2009; 69: 101-13; Toms L, McQuay HJ, Derry S, Moore RA. Single dose oral paracetamol (acetaminophen) for postoperative pain in adults. Cochrane Database Syst Rev 2008: CD004602]. I.V. paracetamol is superior to oral for pain rescue (Jarde O, Boccard E. Parenteral versus oral route increases paracetamol efficacy. Clin Drug Invest 1997; 14: 474-81). By randomized, double-blinded trial, we aimed to determine whether preoperative oral paracetamol provides inferior postoperative analgesia to preoperative i.v. paracetamol. METHODS: One hundred and thirty participants received either oral paracetamol and i.v. placebo (Group OP), or oral placebo and i.v. paracetamol (Perfalgan™) (Group IP). Oral preparations were given at least 45 min before surgery; i.v. preparations after induction of anaesthesia. Pain was assessed by a 100 mm visual analogue scale (VAS) 1 h from the end of surgery. Rescue analgesia was given on request. RESULTS: A total of 128 patients completed the study. There were no significant differences in baseline characteristics or intraoperative variables between the groups. The study was designed to reveal whether OP is inferior to IP, with an inferiority margin of 20%. The number of patients reporting satisfactory analgesia at 1 h with VAS ≤ 30 mm were 15 (OP) and 17 (IP), respectively. The secondary outcome measure of the mean (standard deviation) VAS (mm) for the whole of each group was 52 (22) for OP and 47 (22) for IP. Analysis of confidence intervals indicates that oral paracetamol is not inferior to i.v. paracetamol. The median survival (90% CI) to rescue analgesia request was 54.3 (51.2-57.4) min in Group OP and 57.3 (55.4-59.2) min in Group IP; there was no significant difference in this measure. CONCLUSIONS: In this study of lower third molar extraction, oral paracetamol is not inferior to i.v. for postoperative analgesia. ISRCTN Registration http://www.controlled-trials.com/ISRCTN77607163.

First-order reorientation transition of the flux-line lattice in CaAlSi.

The flux-line lattice in CaAlSi has been studied by small-angle neutron scattering. A well-defined hexagonal flux-line lattice is seen just above H(c1) in an applied field of only 54 Oe. A 30° reorientation of this vortex lattice has been observed in a very low field of 200 Oe. This reorientation transition appears to be first-order and could be explained by nonlocal effects. The magnetic field dependence of the form factor is well-described by a single penetration depth of λ=1496(1) Å and a single coherence length of ξ=307(1) Å at 2 K. At 1.5 K, the penetration depth anisotropy is γ(λ)=2.7(1), with the field applied perpendicular to the c axis, and agrees with the coherence length anisotropy determined from critical field measurements.

Elimination of subterranean termite (Isoptera: Rhinotermitidae) colonies using a refined cellulose bait matrix containing noviflumuron when monitored and replenished quarterly.

Using a quarterly (3-mo) monitoring and bait-replenishment interval, 122 subterranean termite colonies throughout the United States were baited with a refined cellulose bait matrix containing 0.5% noviflumuron. All colonies were eliminated in less than 1 yr after initiation of baiting as determined by long-term monitoring and genetic markers. Sixty-three percent of the colonies were eliminated during the first quarter after the initiation of baiting and 77% of colonies were eliminated after consuming two bait tubes or less. This suggests that a single baiting cycle and bait installed in response to a single active monitoring device were sufficient to eliminate the majority of colonies. Although termites temporarily abandoned stations after depleting bait, workers resumed feeding when baits were replenished. Colonies that consumed large amounts of bait before elimination foraged into multiple stations, thus allowing adequate amounts of bait to sustain feeding. The time to eliminate termite colonies with bait replenished quarterly was similar to that previously reported for laminated cellulose bait replenished monthly. Our data support the conclusion that extending the bait replenishment interval from monthly to quarterly for bait tubes with refined cellulose containing 0.5% noviflumuron did not adversely impact colony elimination.

Magnetic monopole density and antiferromagnetic domain control in spin-ice iridates.

Magnetically frustrated systems provide fertile ground for complex behaviour, including unconventional ground states with emergent symmetries, topological properties, and exotic excitations. A canonical example is the emergence of magnetic-charge-carrying quasiparticles in spin-ice compounds. Despite extensive work, a reliable experimental indicator of the density of these magnetic monopoles is yet to be found. Using measurements on single crystals of Ho2Ir2O7 combined with dipolar Monte Carlo simulations, we show that the isothermal magnetoresistance is highly sensitive to the monopole density. Moreover, we uncover an unexpected and strong coupling between the monopoles on the holmium sublattice and the antiferromagnetically ordered iridium ions. These results pave the way towards a quantitative experimental measure of monopole density and demonstrate the ability to control antiferromagnetic domain walls using a uniform external magnetic field, a key goal in the design of next-generation spintronic devices.

Slow magnetic order-order transition in the spin chain antiferromagnet Ca3Co2O6.

Using powder neutron diffraction, we have discovered an unusual magnetic order-order transition in the Ising spin chain compound Ca3Co2O6. On lowering the temperature, an antiferromagnetic phase with a propagation vector k=(0.5,-0.5,1) emerges from a higher temperature spin density wave structure with k=(0,0,1.01). This transition occurs over an unprecedented time scale of several hours and is never complete.

Investigation of the magnetic ground state of GaV4S8using powder neutron diffraction.

The magnetic ground state of polycrystalline Néel skyrmion hosting material GaV4S8has been investigated usingacsusceptibility and powder neutron diffraction. In the absence of an applied magnetic field GaV4S8undergoes a transition from a paramagnetic to a cycloidal state below 13 K and then to a ferromagnetic-like state below 6 K. With evidence fromacsusceptibility and powder neutron diffraction, we have identified the commensurate magnetic structure at 1.5 K, with ordered magnetic moments of 0.23(2) µBon the V1 sites and 0.22(1) µBon the V2 sites. These moments have ferromagnetic-like alignment but with a 39(8)° canting of the magnetic moments on the V2 sites away from the V4cluster. In the incommensurate magnetic phase that exists between 6 and 13 K, we provide a thorough and careful analysis of the cycloidal magnetic structure exhibited by this material using powder neutron diffraction.

Chiral singlet superconductivity in the weakly correlated metal LaPt3P.

Chiral superconductors are novel topological materials with finite angular momentum Cooper pairs circulating around a unique chiral axis, thereby spontaneously breaking time-reversal symmetry. They are rather scarce and usually feature triplet pairing: a canonical example is the chiral p-wave state realized in the A-phase of superfluid He3. Chiral triplet superconductors are, however, topologically fragile with the corresponding gapless boundary modes only weakly protected against symmetry-preserving perturbations in contrast to their singlet counterparts. Using muon spin relaxation measurements, here we report that the weakly correlated pnictide compound LaPt3P has the two key features of a chiral superconductor: spontaneous magnetic fields inside the superconducting state indicating broken time-reversal symmetry and low temperature linear behaviour in the superfluid density indicating line nodes in the order parameter. Using symmetry analysis, first principles band structure calculation and mean-field theory, we unambiguously establish that the superconducting ground state of LaPt3P is a chiral d-wave singlet.

Evidence for associations between the purinergic receptor P2X(7) (P2RX7) and toxoplasmosis.

Congenital Toxoplasma gondii infection can result in intracranial calcification, hydrocephalus and retinochoroiditis. Acquired infection is commonly associated with ocular disease. Pathology is characterized by strong proinflammatory responses. Ligation of ATP by purinergic receptor P2X(7), encoded by P2RX7, stimulates proinflammatory cytokines and can lead directly to killing of intracellular pathogens. To determine whether P2X(7) has a role in susceptibility to congenital toxoplasmosis, we examined polymorphisms at P2RX7 in 149 child/parent trios from North America. We found association (FBAT Z-scores +/-2.429; P=0.015) between the derived C(+)G(-) allele (f=0.68; OR=2.06; 95% CI: 1.14-3.75) at single-nucleotide polymorphism (SNP) rs1718119 (1068T>C; Thr-348-Ala), and a second synonymous variant rs1621388 in linkage disequilibrium with it, and clinical signs of disease per se. Analysis of clinical subgroups showed no association with hydrocephalus, with effect sizes for associations with retinal disease and brain calcifications enhanced (OR=3.0-4.25; 0.004

Ir 5d-band derived superconductivity in LaIr3.

The superconducting properties of rhombohedral LaIr3 were examined using susceptibility, resistivity, heat capacity, and zero-field (ZF) and transverse-field (TF) muon spin relaxation and rotation ([Formula: see text]SR) measurements. The susceptibility and resistivity measurements confirm a superconducting transition below [Formula: see text] K. Two successive transitions are observed in the heat capacity data, one at [Formula: see text] K and a second at 1.2 K below [Formula: see text]. The heat capacity jump is [Formula: see text], which is lower than 1.43 expected for Bardeen-Cooper-Schrieffer (BCS) weak-coupling limit. TF-[Formula: see text]SR measurements reveal a fully gapped s-wave superconductivity with [Formula: see text], which is small compared to the BCS value of 3.56, suggesting weak-coupling superconductivity. The magnetic penetration depth, [Formula: see text], estimated from TF-[Formula: see text]SR gives [Formula: see text] nm, a superconducting carrier density [Formula: see text] carriers m-3 and a carrier effective-mass enhancement factor [Formula: see text]. ZF-[Formula: see text]SR data show no evidence for any spontaneous magnetic fields below [Formula: see text], which demonstrates that time-reversal symmetry is preserved in the superconducting state of LaIr3.

Investigation of superconducting gap structure in HfIrSi using muon spin relaxation/rotation.

We have investigated the superconducting state of HfIrSi using magnetization, specific heat, muon spin rotation and relaxation ([Formula: see text]SR) measurements. Superconductivity was observed at [Formula: see text] K in both specific heat and magnetization measurements. From an analysis of the transverse-field [Formula: see text]SR data, it is clear that the temperature variation of superfluid density is well fitted by an isotropic Bardeen-Cooper-Schrieffer (BCS) type s-wave gap structure. The superconducting carrier density [Formula: see text] m-3, the magnetic penetration depth, [Formula: see text] nm, and the effective mass, [Formula: see text], were calculated from the TF-[Formula: see text]SR data. Zero-field [Formula: see text]SR data for HfIrSi reveal the absence of any spontaneous magnetic moments below [Formula: see text], indicating that time-reversal symmetry (TRS) is preserved in the superconducting state of HfIrSi. Theoretical investigations suggest that the Hf and Ir atoms hybridize strongly along the c-axis, and that this is responsible for the strong three-dimensionality of this system which screens the Coulomb interaction. As a result, despite the presence of d-electrons in HfIrSi, these correlation effects are weakened, making the electron-phonon coupling more important.