Microfluidic out-of-equilibrium control of molecular nanotubes

The bottom-up fabrication of functional nanosystems for light-harvesting applications and excitonic devices often relies on molecular self-assembly. Gaining access to the intermediate species involved in self-assembly would provide valuable insights into the pathways via which the final architecture has evolved, yet difficult to achieve due to their intrinsically short-lived nature. Here, we employ a lab-on-a-chip approach as a means to obtain in situ control of the structural complexity of an artificial light-harvesting complex: molecular double-walled nanotubes. Rapid and stable dissolution of the outer wall was realized via microfluidic mixing thereby rendering the thermodynamically unstable inner tubes accessible to spectroscopy. By measurement of the linear dichroism and time-resolved photoluminescence of both double-walled nanotubes and isolated inner tubes we show that the optical (excitonic) properties of the inner tube are remarkably robust to such drastic perturbation of the system's supramolecular structure as removal of the outer wall. The developed platform is readily extendable to a broad range of practical applications such as e.g. self-assembling systems and molecular photonics devices

Reproducibility and responsiveness of the Frailty Index and Frailty Phenotype in older hospitalized patients

BACKGROUND: There is growing interest for interventions aiming at preventing frailty progression or even to reverse frailty in older people, yet it is still unclear which frailty instrument is most appropriate for measuring change scores over time to determine the effectiveness of interventions. The aim of this prospective cohort study was to determine reproducibility and responsiveness properties of the Frailty Index (FI) and Frailty Phenotype (FP) in acutely hospitalized medical patients aged 70 years and older. METHODS: Reproducibility was assessed by Intra-Class Correlation Coefficients (ICC), standard error of measurement (SEM) and smallest detectable change (SDC); Responsiveness was assessed by the standardized response mean (SRM), and area under the receiver operating characteristic curve (AUC). RESULTS: At baseline, 243 patients were included with a median age of 76 years (range 70–98). The analytic samples included 192 and 187 patients in the three and twelve months follow-up analyses, respectively. ICC of the FI were 0.85 (95 % confidence interval [CI]: 0.76; 0.91) and 0.84 (95% CI: 0.77; 0.90), and 0.65 (95% CI: 0.49; 0.77) and 0.77 (95% CI: 0.65; 0.84) for the FP. SEM ranged from 5 to 13 %; SDC from 13 to 37 %. SRMs were good in patients with unchanged frailty status (< 0.50), and doubtful to good for deteriorated and improved patients (0.43–1.00). AUC’s over three months were 0.77 (95% CI: 0.69; 0.86) and 0.71 (95% CI: 0.62; 0.79) for the FI, and 0.68 (95% CI: 0.58; 0.77) and 0.65 (95% CI: 0.55; 0.74) for the FP. Over twelve months, AUCs were 0.78 (95% CI: 0.69; 0.87) and 0.82 (95% CI: 0.73; 0.90) for the FI, and 0.78 (95% CI: 0.69; 0.87) and 0.75 (95% CI: 0.67; 0.84) for the FP. CONCLUSIONS: The Frailty Index showed better reproducibility and responsiveness properties compared to the Frailty Phenotype among acutely hospitalized older patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12877-021-02444-y

An angle-scanned cryogenic Fabry-Pérot interferometer for far-infrared astronomy

The sensitivity of state-of-the-art superconducting far-infrared detectors used in conjunction with cryogenically cooled space telescopes and instrumentation is such that spectroscopic observations are generally limited by photon noise from the astronomical source or by galactic foreground or zodiacal emission within the field-of-view. Therefore, an instrument design that restricts the spectral bandpass viewed by the detector must be employed. One method of achieving background limited, high resolution spectroscopy is to combine a high resolution component such as a Fabry–Pérot interferometer (FPI) with a lower resolution, post-dispersing system, such as a grating spectrometer, the latter serving to restrict the spectral bandpass. The resonant wavelength of an FPI is most often tuned by changing the spacing or medium between the parallel reflecting plates of the etalon. In this paper, we present a novel design for an FPI in which the wavelength is tuned by scanning the angle of incidence on a high refractive index etalon. This concept simplifies the cryomechanical design, actuation, and metrology. The first results from the realized instrument are presented and compared with theory. The effects on the spectral response as a function of the incident angle have been simulated and shown to agree well with the observation

First light results from a novel cryogenic Fabry-Pérot interferometer

The sensitivity of state-of-the-art superconducting far-infrared detectors is such that astronomical observations at these wavelengths are limited by photon noise from the astronomical source unless a method of restricting the spectral bandpass is employed. One such method is to use a high resolution Fabry-Perot interferometer (FPI) in conjunction with a lower resolution, post-dispersing system, such as a grating spectrometer. The resonant wavelength of an FPI is typically tuned by changing the spacing or medium between the parallel reflecting plates of the etalon. We previously reported on a novel design in which the wavelength is tuned by scanning the angle of incidence, which simplifies the cryo-mechanical design, actuation and metrology. Here we present first light results from the realized instrument

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10−5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10−06/Pfemales: 3.45 × 10−07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation