Phononically shielded photonic-crystal mirror membranes for cavity quantum optomechanics.

We present a highly reflective, sub-wavelength-thick membrane resonator featuring high mechanical quality factor and discuss its applicability for cavity optomechanics. The 88.5 nm thin stoichiometric silicon-nitride membrane, designed and fabricated to combine 2D-photonic and phononic crystal patterns, reaches reflectivities up to 99.89 % and a mechanical quality factor of 2.9 × 107 at room temperature. We construct a Fabry-Perot-type optical cavity, with the membrane forming one terminating mirror. The optical beam shape in cavity transmission shows a stark deviation from a simple Gaussian mode-shape, consistent with theoretical predictions. We demonstrate optomechanical sideband cooling to mK-mode temperatures, starting from room temperature. At higher intracavity powers we observe an optomechanically induced optical bistability. The demonstrated device has potential to reach high cooperativities at low light levels desirable, for example, for optomechanical sensing and squeezing applications or fundamental studies in cavity quantum optomechanics; and meets the requirements for cooling to the quantum ground state of mechanical motion from room temperature.

Subjective and psychophysical olfactory and gustatory dysfunction among COVID-19 outpatients; short- and long-term results.

BACKGROUND: Olfactory and gustatory dysfunctions are early symptoms of SARS-CoV-2 infection. Between 20-80% of infected individuals report subjective altered sense of smell and/or taste during infection. Up to 2/3 of previously infected experience persistent olfactory and/or gustatory dysfunction after 6 months. The aim of this study was to examine subjective and psychophysical olfactory and gustatory function in non-hospitalized individuals with acute COVID-19 up to 6 months after infection. METHODS: Individuals aged 18-80-years with a positive SARS-CoV-2 PCR test no older than 10 days, were eligible. Only individuals able to visit the outpatient examination facilities were included. Gustatory function was tested with the Burgharts Taste Strips and olfactory function was examined with the Brief Smell Identifications test (Danish version). Subjective symptoms were examined through an online questionnaire at inclusion, day 30, 90 and 180 after inclusion. RESULTS: Fifty-eight SARS-CoV-2 positive and 56 negative controls were included. 58.6% (34/58) of SARS-CoV-2 positive individuals vs. 8.9% (5/56) of negative controls reported subjective olfactory dysfunction at inclusion. For gustatory dysfunction, 46.5% (27/58) of positive individuals reported impairment compared to 8.9% (5/56) of negative controls. In psychophysical tests, 75.9% (46/58) had olfactory dysfunction and 43.1% (25/58) had gustatory dysfunction among the SARS-CoV-2 positive individuals at inclusion. Compared to negative controls, SARS-CoV-2 infected had significantly reduced olfaction and gustation. Previously infected individuals continued to report lower subjective sense of smell 30 days after inclusion, whereafter the difference between the groups diminished. However, after 180 days, 20.7% (12/58) positive individuals still reported reduced sense of smell and taste. CONCLUSION: Olfactory and gustatory dysfunctions are prevalent symptoms of SARS-CoV-2 infection, but there is inconsistency between subjective reporting and psychophysical test assessment of especially olfaction. Most individuals regain normal function after 30 days, but approximately 20% report persistent olfactory and gustatory dysfunction 6 months after infection.

Listeria Monocytogenes Brain Abscesses in a Patient with Disseminated Non-Small Cellular Lung Cancer: MRI Findings.

Brain abscesses caused by Listeria monocytogenes (LM) are very rare and carry a high mortality risk. We present a patient with disseminated non-small cellular lung cancer (NSCLC) and multiple unusual LM brain abscesses. These abscesses have multiple elongated peripherally enhancing lesions in a characteristic formation that is "worm or tramtrack-like" following the white matter fiber tracts.

Cross-sectional study of medical advertisements in a national general medical journal: evidence, cost, and safe use of advertised versus comparative drugs.

BACKGROUND: Healthcare professionals are exposed to advertisements for prescription drugs in medical journals. Such advertisements may increase prescriptions of new drugs at the expense of older treatments even when they have no added benefits, are more harmful, and are more expensive. The publication of medical advertisements therefore raises ethical questions related to editorial integrity. METHODS: We conducted a descriptive cross-sectional study of all medical advertisements published in the Journal of the Danish Medical Association in 2015. Drugs advertised 6 times or more were compared with older comparators: (1) comparative evidence of added benefit; (2) Defined Daily Dose cost; (3) regulatory safety announcements; and (4) completed and ongoing post-marketing studies 3 years after advertising. RESULTS: We found 158 medical advertisements for 35 prescription drugs published in 24 issues during 2015, with a median of 7 advertisements per issue (range 0 to 11). Four drug groups and 5 single drugs were advertised 6 times or more, for a total of 10 indications, and we made 14 comparisons with older treatments. We found: (1) 'no added benefit' in 4 (29%) of 14 comparisons, 'uncertain benefits' in 7 (50%), and 'no evidence' in 3 (21%) comparisons. In no comparison did we find evidence of 'substantial added benefit' for the new drug; (2) advertised drugs were 2 to 196 times (median 6) more expensive per Defined Daily Dose; (3) 11 safety announcements for five advertised drugs were issued compared to one announcement for one comparator drug; (4) 20 post-marketing studies (7 completed, 13 ongoing) were requested for the advertised drugs versus 10 studies (4 completed, 6 ongoing) for the comparator drugs, and 7 studies (2 completed, 5 ongoing) assessed both an advertised and a comparator drug at 3 year follow-up. CONCLUSIONS AND RELEVANCE: In this cross-sectional study of medical advertisements published in the Journal of the Danish Medical Association during 2015, the most advertised drugs did not have documented substantial added benefits over older treatments, whereas they were substantially more expensive. From January 2021, the Journal of the Danish Medical Association no longer publishes medical advertisements.

Sensitive optomechanical transduction of electric and magnetic signals to the optical domain.

We report a radio-frequency-to-optical converter based on an electro-optomechanical transduction scheme where the electrical, optical, and mechanical interface was integrated on a chip and operated with a fiber-coupled optical setup. The device was designed for field tests in a magnetic resonance scanner where its small form-factor and simple operation is paramount. For the appurtenant magnetic resonance detection circuit at 32 MHz, we demonstrate transduction with an intrinsic magnetic field sensitivity of 8 fT/Hz, noise figure 2.3 dB, noise temperature 210 K, voltage noise 99 pV/Hz, and current noise 113 pA/Hz, all in a 3 dB-bandwidth of 12 kHz. Such sensitivity and bandwidth make the transducer a valuable alternative to conventional electronic preamplifiers that additionally is directly compatible with fiber communication networks.

Impaired reproduction after exposure to ADHD drugs: Systematic review of animal studies.

BACKGROUND: Few studies have reported on long-term harms caused by ADHD drugs but they are known to impair growth. OBJECTIVE: To assess whether ADHD drugs impair reproduction in mammals. METHODS: Systematic review of reproduction in studies of animals treated with ADHD drugs. DATA SOURCES: PubMed, Biosis and EMBASE. RESULTS: We included 17 studies. The studies were generally of poor quality or poorly reported. Two studies reported the use of one of three advised randomisation methods. Fifteen studies used placebo which suggested blinding. On clonidine, the ability to produce offspring was reduced for male rats, which approached two females each. In one study, 10 treated rats produced no offspring while all four controls did. In another study, 10 treated rats impregnated nine females while 10 controls impregnated 16. On methylphenidate, vaginal opening was delayed in two studies (in one, the mean difference was 4.0 days, 95% CI 2.5 to 5.6, and number of estrous cycles was halved; in the other, the minimum delay was 6 days), while in two other studies no difference occurred. Generally, the impairments improved after a drug-free period and were less pronounced when treatment started later in life. CONCLUSION: ADHD drugs impair the reproduction in animals.

Persistent sexual dysfunction after early exposure to SSRIs: Systematic review of animal studies.

BACKGROUND: Sexual dysfunction is a common adverse effect of selective serotonin reuptake inhibitors (SSRIs) and there is a concern that the sexual harms might persist after discontinuation of therapy. OBJECTIVE: To assess whether the use of SSRIs in animals can lead to persistent sexual dysfunction. METHODS: Systematic review of animal studies measuring sexual behaviour after end of treatment with SSRIs or serotonin norepinephrine reuptake inhibitors. DATA SOURCES: We searched PubMed and EMBASE. RESULTS: We included 14 studies. The general quality of the studies was poor. Only four studies reported use of randomisation and none mentioned allocation concealment. All studies used placebo and were therefore blinded. For rats exposed to SSRIs compared with those exposed to placebo, we found a higher risk of no mounting behaviour (RR = 0.73; 95% CI = 0.62-0.86), no intromission behaviour (RR = 0.74; 95% CI = 0.60-0.92) and no ejaculation behaviour (RR = 0.49, 95% CI = 0.24-1.00). CONCLUSION: Our results showed substantial and lasting effects on sexual behaviour in rats after exposure to an SSRI early in life on important sexual outcomes.

Demonstration of suppressed phonon tunneling losses in phononic bandgap shielded membrane resonators for high-Q optomechanics.

Dielectric membranes with exceptional mechanical and optical properties present one of the most promising platforms in quantum opto-mechanics. The performance of stressed silicon nitride nanomembranes as mechanical resonators notoriously depends on how their frame is clamped to the sample mount, which in practice usually necessitates delicate, and difficult-to-reproduce mounting solutions. Here, we demonstrate that a phononic bandgap shield integrated in the membrane's silicon frame eliminates this dependence, by suppressing dissipation through phonon tunneling. We dry-etch the membrane's frame so that it assumes the form of a cm-sized bridge featuring a 1-dimensional periodic pattern, whose phononic density of states is tailored to exhibit one, or several, full band gaps around the membrane's high-Q modes in the MHz-range. We quantify the effectiveness of this phononic bandgap shield by optical interferometry measuring both the suppressed transmission of vibrations, as well as the influence of frame clamping conditions on the membrane modes. We find suppressions up to 40 dB and, for three different realized phononic structures, consistently observe significant suppression of the dependence of the membrane's modes on sample clamping-if the mode's frequency lies in the bandgap. As a result, we achieve membrane mode quality factors of 5 × 10(6) with samples that are tightly bolted to the 8 K-cold finger of a cryostat. Q × f -products of 6 × 10(12) Hz at 300 K and 14 × 10(12) Hz at 8 K are observed, satisfying one of the main requirements for optical cooling of mechanical vibrations to their quantum ground-state.

Interaction of peptidomimetics with bilayer membranes: biophysical characterization and cellular uptake.

Enzymatically stable cell-penetrating α-peptide/ß-peptoid peptidomimetics constitute promising drug delivery vehicles for the transport of therapeutic biomacromolecules across membrane barriers. The aim of the present study was to elucidate the mechanism of peptidomimetic-lipid bilayer interactions. A series of peptidomimetics consisting of alternating cationic and hydrophobic residues displaying variation in length and N-terminal end group were applied to fluid-phase, anionic lipid bilayers, and their interaction was investigated using isothermal titration calorimetry (ITC) and ellipsometry. Titration of lipid vesicles into solutions of peptidomimetics resulted in exothermic adsorption processes, and the interaction of all studied peptidomimetics with anionic lipid membranes was found to be enthalpy-driven. The enthalpy and Gibbs free energy (ΔG) proved more favorable with increasing chain length. However, not all charges contribute equally to the interaction, as evidenced by the charge-normalized ΔG being inversely correlated to the sequence length. Ellipsometry data suggested that the hydrophobic residues also played an important role in the interaction process. Furthermore, ΔG extracted from ellipsometry data showed good agreement with that obtained with ITC. To further elucidate their interaction with biological membranes, quantitative uptake and cellular distribution were studied in proliferating HeLa cells by flow cytometry and confocal microscopy. The cellular uptake of carboxyfluorescein-labeled peptidomimetics showed a similar ranking as that obtained from the adsorbed amount, and binding energy to model membranes demonstrated that the initial interaction with the membrane is of key importance for the cellular uptake.