All-optical subcycle microscopy on atomic length scales.

Bringing optical microscopy to the shortest possible length and time scales has been a long-sought goal, connecting nanoscopic elementary dynamics with the macroscopic functionalities of condensed matter. Super-resolution microscopy has circumvented the far-field diffraction limit by harnessing optical nonlinearities1. By exploiting linear interaction with tip-confined evanescent light fields2, near-field microscopy3,4 has reached even higher resolution, prompting a vibrant research field by exploring the nanocosm in motion5-19. Yet the finite radius of the nanometre-sized tip apex has prevented access to atomic resolution20. Here we leverage extreme atomic nonlinearities within tip-confined evanescent fields to push all-optical microscopy to picometric spatial and femtosecond temporal resolution. On these scales, we discover an unprecedented and efficient non-classical near-field response, in phase with the vector potential of light and strictly confined to atomic dimensions. This ultrafast signal is characterized by an optical phase delay of approximately π/2 and facilitates direct monitoring of tunnelling dynamics. We showcase the power of our optical concept by imaging nanometre-sized defects hidden to atomic force microscopy and by subcycle sampling of current transients on a semiconducting van der Waals material. Our results facilitate access to quantum light-matter interaction and electronic dynamics at ultimately short spatio-temporal scales in both conductive and insulating quantum materials.

Nanosilver/DCOIT-containing surface coating effectively and constantly reduces microbial load in emergency room surfaces.

BACKGROUND: Colonization of near-patient surfaces in hospitals plays an important role as a source of healthcare-associated infections. Routine disinfection methods only result in short-term elimination of pathogens. AIM: To investigate the efficiency of a newly developed antimicrobial coating containing nanosilver in long-term reduction of bacterial burden in hospital surfaces to close the gap between routine disinfection cycles. METHODS: In this prospective, double-blinded trial, frequently touched surfaces of a routinely used treatment room in an emergency unit of a level-I hospital were treated with a surface coating (nanosilver/DCOIT-coated surface, NCS) containing nanosilver particles and another organic biocidal agent (4,5-dichloro-2-octyl-4-isothiazolin-3-one, DCOIT), whereas surfaces of another room were treated with a coating missing both the nanosilver- and DCOIT-containing ingredient and served as control. Bacterial contamination of the surfaces was examined using contact plates and liquid-based swabs daily for a total trial duration of 90 days. After incubation, total microbial counts and species were assessed. FINDINGS: In a total of 2880 antimicrobial samples, a significant reduction of the overall bacterial load was observed in the NCS room (median: 0.31 cfu/cm2; interquartile range: 0.00-1.13) compared with the control coated surfaces (0.69 cfu/cm2; 0.06-2.00; P < 0.001). The nanosilver- and DCOIT-containing surface coating reduced the relative risk of a critical bacterial load (defined as >5 cfu/cm2) by 60% (odds ratio 0.38, P < 0.001). No significant difference in species distribution was detected between NCS and control group. CONCLUSION: Nanosilver-/DCOIT-containing surface coating has shown efficiency for sustainable reduction of bacterial load of frequently touched surfaces in a clinical setting.

Direct observation of vortices in an electron fluid.

Vortices are the hallmarks of hydrodynamic flow. Strongly interacting electrons in ultrapure conductors can display signatures of hydrodynamic behaviour, including negative non-local resistance1-4, higher-than-ballistic conduction5-7, Poiseuille flow in narrow channels8-10 and violation of the Wiedemann-Franz law11. Here we provide a visualization of whirlpools in an electron fluid. By using a nanoscale scanning superconducting quantum interference device on a tip12, we image the current distribution in a circular chamber connected through a small aperture to a current-carrying strip in the high-purity type II Weyl semimetal WTe2. In this geometry, the Gurzhi momentum diffusion length and the size of the aperture determine the vortex stability phase diagram. We find that vortices are present for only small apertures, whereas the flow is laminar (non-vortical) for larger apertures. Near the vortical-to-laminar transition, we observe the single vortex in the chamber splitting into two vortices; this behaviour is expected only in the hydrodynamic regime and is not anticipated for ballistic transport. These findings suggest a new mechanism of hydrodynamic flow in thin pure crystals such that the spatial diffusion of electron momenta is enabled by small-angle scattering at the surfaces instead of the routinely invoked electron-electron scattering, which becomes extremely weak at low temperatures. This surface-induced para-hydrodynamics, which mimics many aspects of conventional hydrodynamics including vortices, opens new possibilities for exploring and using electron fluidics in high-mobility electron systems.

Heat stress in Africa under high intensity climate change.

Extreme weather events are major causes of loss of life and damage infrastructure worldwide. High temperatures cause heat stress on humans, livestock, crops and infrastructure. Heat stress exposure is projected to increase with ongoing climate change. Extremes of temperature are common in Africa and infrastructure is often incapable of providing adequate cooling. We show how easily accessible cooling technology, such as evaporative coolers, prevent heat stress in historic timescales but are unsuitable as a solution under climate change. As temperatures increase, powered cooling, such as air conditioning, is necessary to prevent overheating. This will, in turn, increase demand on already stretched infrastructure. We use high temporal resolution climate model data to estimate the demand for cooling according to two metrics, firstly the apparent temperature and secondly the discomfort index. For each grid cell we calculate the heat stress value and the amount of cooling required to turn a heat stress event into a non heat stress event. We show the increase in demand for cooling in Africa is non uniform and that equatorial countries are exposed to higher heat stress than higher latitude countries. We further show that evaporative coolers are less effective in tropical regions than in the extra tropics. Finally, we show that neither low nor high efficiency coolers are sufficient to return Africa to current levels of heat stress under climate change.

Feasibility, pitfalls and results of a structured concept-development phase for a randomized controlled phase III trial on radiotherapy in primary prostate cancer patients.

OBJECTIVE: Failure rate in randomized controlled trials (RCTs) is > 50%, includes safety-problems, underpowered statistics, lack of efficacy, lack of funding or insufficient patient recruitment and is even more pronounced in oncology trials. We present results of a structured concept-development phase (CDP) for a phase III RCT on personalized radiotherapy (RT) in primary prostate cancer (PCa) patients implementing prostate specific membrane antigen targeting positron emission tomography (PSMA-PET). MATERIALS AND METHODS: The 1 yr process of the CDP contained five main working packages: (i) literature search and scoping review, (ii) involvement of individual patients, patients' representatives and patients' self-help groups addressing the patients' willingness to participate in the preparation process and the conduct of RCTs as well as the patient informed consent (PIC), (iii) involvement of national and international experts and expert panels (iv) a phase II pilot study investigating the safety of implementation of PSMA-PET for focal dose escalation RT and (v) in-silico RT planning studies assessing feasibility of envisaged dose regimens and effects of urethral sparing in focal dose escalation. RESULTS: (i) Systematic literature searches confirmed the high clinical relevance for more evidence on advanced RT approaches, in particular stereotactic body RT, in high-risk PCa patients. (ii) Involvement of patients, patient representatives and randomly selected males relevantly changed the PIC and initiated a patient empowerment project for training of bladder preparation. (iii) Discussion with national and international experts led to adaptions of inclusion and exclusion criteria. (iv) Fifty patients were treated in the pilot trial and in- and exclusion criteria as well as enrollment calculations were adapted accordingly. Parallel conduction of the pilot trial revealed pitfalls on practicability and broadened the horizon for translational projects. (v) In-silico planning studies confirmed feasibility of envisaged dose prescription. Despite large prostate- and boost-volumes of up to 66% of the prostate, adherence to stringent anorectal dose constraints was feasible. Urethral sparing increased the therapeutic ratio. CONCLUSION: The dynamic framework of interdisciplinary working programs in CDPs enhances robustness of RCT protocols and may be associated with decreased failure rates. Structured recommendations are warranted to further define the process of such CDPs in radiation oncology trials.

Five-year audit of adherence to an anaesthesia pre-induction checklist.

Although patient safety related to airway management has improved substantially over the last few decades, life-threatening events still occur. Technical skills, clinical expertise and human factors contribute to successful airway management. Checklists aim to improve safety by providing a structured approach to equipment, personnel and decision-making. This audit investigates adherence to our institution's airway checklist from 1 June 2016 to 31 May 2021. Inclusion criteria were procedures requiring airway management and we excluded all procedures performed solely under regional anaesthesia, sedation without airway management or paediatric and cardiovascular surgery. The primary outcome was the proportion of wholly performed pre-induction checklists. Secondary outcomes were the pattern of adherence over the 5 years well as details of airway management, including: airway management difficulties; time and location of induction; anaesthesia teams in operating theatres (including teams for different surgical specialities); non-operating theatre and emergency procedures; type of anaesthesia (general or combined); and urgency of the procedure. In total, 95,946 procedures were included. In 57.3%, anaesthesia pre-induction checklists were completed. Over the 5 years after implementation, adherence improved from 48.3% to 66.7% (p < 0.001). Anticipated and unanticipated airway management difficulties (e.g. facemask ventilation, supraglottic airway device or intubation) defined by the handling anaesthetist were encountered in 4.2% of all procedures. Completion of the checklist differed depending on the time of day (61.3% during the day vs. 35.0% during the night, p < 0.001). Completion also differed depending on location (66.8% in operating theatres vs. 41.0% for non-operating theatre anaesthesia, p < 0.001) and urgency of procedure (65.4% in non-emergencies vs. 35.4% in emergencies, p < 0.001). A mixed-effect model indicated that urgency of procedure is a strong predictor for adherence, with emergency cases having lower adherence (OR 0.58, 95%CI 0.49-0.68, p < 0.001). In conclusion, over 5 years, a significant increase in adherence to an anaesthesia pre-induction checklist was found, and areas for further improvement (e.g. emergencies, non-operating room procedures, night-time procedures) were identified.

Constraints on Lightly Ionizing Particles from CDMSlite.

The Cryogenic Dark Matter Search low ionization threshold experiment (CDMSlite) achieved efficient detection of very small recoil energies in its germanium target, resulting in sensitivity to lightly ionizing particles (LIPs) in a previously unexplored region of charge, mass, and velocity parameter space. We report first direct-detection limits calculated using the optimum interval method on the vertical intensity of cosmogenically produced LIPs with an electric charge smaller than e/(3×10^{5}), as well as the strongest limits for charge ≤e/160, with a minimum vertical intensity of 1.36×10^{-7} cm^{-2} s^{-1} sr^{-1} at charge e/160. These results apply over a wide range of LIP masses (5 MeV/c^{2} to 100 TeV/c^{2}) and cover a wide range of ßγ values (0.1-10^{6}), thus excluding nonrelativistic LIPs with ßγ as small as 0.1 for the first time.

Light Dark Matter Search with a High-Resolution Athermal Phonon Detector Operated above Ground.

We present limits on spin-independent dark matter-nucleon interactions using a 10.6 g Si athermal phonon detector with a baseline energy resolution of σ_{E}=3.86±0.04(stat)_{-0.00}^{+0.19}(syst) eV. This exclusion analysis sets the most stringent dark matter-nucleon scattering cross-section limits achieved by a cryogenic detector for dark matter particle masses from 93 to 140 MeV/c^{2}, with a raw exposure of 9.9 g d acquired at an above-ground facility. This work illustrates the scientific potential of detectors with athermal phonon sensors with eV-scale energy resolution for future dark matter searches.

Imaging orbital ferromagnetism in a moiré Chern insulator.

Electrons in moiré flat band systems can spontaneously break time-reversal symmetry, giving rise to a quantized anomalous Hall effect. In this study, we use a superconducting quantum interference device to image stray magnetic fields in twisted bilayer graphene aligned to hexagonal boron nitride. We find a magnetization of several Bohr magnetons per charge carrier, demonstrating that the magnetism is primarily orbital in nature. Our measurements reveal a large change in the magnetization as the chemical potential is swept across the quantum anomalous Hall gap, consistent with the expected contribution of chiral edge states to the magnetization of an orbital Chern insulator. Mapping the spatial evolution of field-driven magnetic reversal, we find a series of reproducible micrometer-scale domains pinned to structural disorder.

Neutron sub-micrometre tomography from scattering data.

Neutrons are valuable probes for various material samples across many areas of research. Neutron imaging typically has a spatial resolution of larger than 20 µm, whereas neutron scattering is sensitive to smaller features but does not provide a real-space image of the sample. A computed-tomography technique is demonstrated that uses neutron-scattering data to generate an image of a periodic sample with a spatial resolution of ∼300 nm. The achieved resolution is over an order of magnitude smaller than the resolution of other forms of neutron tomography. This method consists of measuring neutron diffraction using a double-crystal diffractometer as a function of sample rotation and then using a phase-retrieval algorithm followed by tomographic reconstruction to generate a map of the sample's scattering-length density. Topological features found in the reconstructions are confirmed with scanning electron micrographs. This technique should be applicable to any sample that generates clear neutron-diffraction patterns, including nanofabricated samples, biological membranes and magnetic materials, such as skyrmion lattices.

Intraoperative optical coherence tomographic findings in patients undergoing subretinal gene therapy surgery.

BACKGROUND: To analyze intraoperative OCT (iOCT) findings during subretinal gene therapy. METHODS: A single-center, retrospective, observational, case series study of twenty one eyes submitted to subretinal gene therapy. Intrasurgical high definition videos were included for analyzes. Cases with absence of iOCT video or unsuccessful bleb creation were excluded. Sharp needle tip (SNT) or blunted needle tip (BNT) and their interaction with neurosensory retina were evaluated. Presence of subretinal air bubbles, visible opened retinotomy, and medication reflux were also correlated and analyzed. RESULTS: Nineteen of twenty-one eyes were included. Of the two excluded eyes, subretinal bleb creation was unsuccessful in one and technical issues prevented OCT image acquisition in the other. Immediately before subretinal injection, needle indention/penetration of the neurosensory retina with temporary indentation of the RPE/choroid was evident in 16 (84%) of the 19 eyes. Complete RPE/choroid indentation was needed with BNT use compared to SNT (p = 0.0114). An open retinotomy was identified in 14 (74%) of 19 eyes at the conclusion of bleb injection and was more commonly associated with SNT (p = 0.0108). CONCLUSIONS: iOCT provides valuable real-time feedback of cross-sectional retinal anatomy during subretinal gene therapy surgeries. The type of needle tip and its use during the gene therapy procedure seems to influence in the bleb creation and presence of visible open retinotomy. Further studies of iOCT findings during gene therapy delivery procedures are likely to help refine the surgical technique.

SQUID-on-tip with single-electron spin sensitivity for high-field and ultra-low temperature nanomagnetic imaging.

Scanning nanoscale superconducting quantum interference devices (nanoSQUIDs) are of growing interest for highly sensitive quantitative imaging of magnetic, spintronic, and transport properties of low-dimensional systems. Utilizing specifically designed grooved quartz capillaries pulled into a sharp pipette, we have fabricated the smallest SQUID-on-tip (SOT) devices with effective diameters down to 39 nm. Integration of a resistive shunt in close proximity to the pipette apex combined with self-aligned deposition of In and Sn, has resulted in SOTs with a flux noise of 42 nΦ0 Hz-1/2, yielding a record low spin noise of 0.29 µB Hz-1/2. In addition, the new SOTs function at sub-Kelvin temperatures and in high magnetic fields of over 2.5 T. Integrating the SOTs into a scanning probe microscope allowed us to image the stray field of a single Fe3O4 nanocube at 300 mK. Our results show that the easy magnetization axis direction undergoes a transition from the 〈111〉 direction at room temperature to an in-plane orientation, which could be attributed to the Verwey phase transition in Fe3O4.

Precision Measurement of the Neutron Scattering Length of

We report a 0.08% measurement of the bound neutron scattering length of ^{4}He using neutron interferometry. The result is b=(3.0982±0.0021[stat]±0.0014[syst]) fm. The corresponding free atomic scattering length is a=(2.4746±0.0017[stat]±0.0011[syst]) fm. With this result the world average becomes b=(3.0993±0.0025) fm, a 2% downward shift and a reduction in uncertainty by more than a factor of six. Our result is in disagreement with a previous neutron interferometric measurement but is in good agreement with earlier measurements using neutron transmission.

Novel photodynamic coating reduces the bioburden on near-patient surfaces thereby reducing the risk for onward pathogen transmission: a field study in two hospitals.

BACKGROUND: Near-patient surfaces are recognized as a source for hospital-acquired infections. Such surfaces act as reservoirs for microbial contamination by which pathogens can be transmitted from colonized or infected patients to susceptible patients. Routine disinfection of surfaces only results in a temporal elimination of pathogens, and recontamination inevitably occurs shortly between disinfections. AIM: A novel antimicrobial coating based on photodynamics was tested under laboratory conditions and subsequently in a field study in two hospitals under real-life conditions. METHODS: Identical surfaces received a photodynamic or control coating. Bacterial counts [colony-forming units (cfu)/cm2) were assessed regularly for up to 6 months. FINDINGS: The laboratory study revealed a mean reduction of several human pathogens of up to 4.0 ± 0.3 log10. The field study in near-patient environments demonstrated mean bacterial values of 6.1 ± 24.7 cfu/cm2 on all control coatings. Photodynamic coatings showed a significantly lower mean value of 1.9 ± 2.8 cfu/cm2 (P<0.001). When considering benchmarks of 2.5 cfu/cm2 or 5 cfu/cm2, the relative risk for high bacterial counts on surfaces was reduced by 48% (odds ratio 0.38, P<0.001) or 67% (odds ratio 0.27, P<0.001), respectively. CONCLUSION: Photodynamic coatings provide a significant and lasting reduction of bacterial counts on near-patient surfaces, particularly for high bacterial loads, in addition to routine hygiene. The promising results of this proof-of-concept study highlight the need for further studies to determine how this novel technology is correlated with the frequency of hospital-acquired infections.

Multimodal imaging of ring 14 syndrome associated maculopathy.

Background: Ring 14 syndrome is a rare chromosomal disorder characterized by a ring-shaped appearance of chromosome 14. Classically findings include distinct facial characteristics, refractory epilepsy, global development delay, muscular hypotonia and ocular abnormalities. Here we report a retinal multimodal imaging analyses of a ring chromosome 14 syndrome patient with associated macular pigmentary changes.Materials and Methods: Case report of an 11-year-old female with a history of refractory epilepsy since 3 months of age was diagnosed with ring 14 syndrome after karyotype at 8 months old. She presented with muscle weakness, mild intellectual delay, associated hyperopia and punctiform yellowish lesions. Multimodal imaging including fundus photography, red-free fundus photography, fundus auto-fluorescence and spectral-domain optical coherence tomography were used to assess this patient.Results: An 11-year-old female with ring 14 syndrome caused by the fusion of terminal breakpoints in both the short arm and long arm of chromosome 14 at p11.1 and q32.3, respectively. At eye exam, the best corrected visual acuity was 20/20 at both eyes with associated hyperopia. Macula showing scattered punctiform yellowish lesions, bright on red-free fundus photography and hyperautofluorescence dots in the same area. The SD-OCT showed normal characteristics at both eyes with the exception of localized irregularity of the RPE in an area associated with a macular yellow dots.Conclusions: Ring 14 syndrome can cause hyperopia and associated macular yellow dots visible at multimodal imaging analyses. Our data support regular eye examination for all patients with ring chromosome 14 syndrome.

Tracking amyloid oligomerization with monomer resolution using a 13-amino acid peptide with a backbone-fixed spin label.

Amyloid oligomers are suspected as toxic agents in neurodegenerative disease, and are transient and often heterogeneous, making them difficult to detect. Here we show an approach to track the development of amyloid oligomers in situ by room temperature, continuous wave (cw) 9 and 95 GHz EPR. Three amyloid peptides with the 2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid (TOAC) spin label were synthesized by solid phase peptide synthesis: T0EZ (TKVKVLGDVIEVGG) with TOAC (T) at the N-terminus, T5EZ with TOAC in the middle (KVKVTGDVIEVG) and T12EZ with TOAC at the C-terminus (KVKVLGDVIEVTG). These sequences are derived from the K11V (KVKVLGDVIEV) amyloid peptide, which self-aggregates to oligomers with a ß-sheet configuration (A. Laganowsky, et al., Science, 2012, 335, 1228-1231). To monitor oligomerization, the rotational correlation time (τr) is measured by cw-EPR. For the backbone-fixed TOAC label that is devoid of local mobility τr should reflect the rotation and thereby the size of the peptide, resp. oligomer. For T5EZ a good match between the measured τr and the size of the peptide is obtained, showing the validity of the approach. One of the three peptides (T0EZ) aggregates (circular dichroism), whereas the other two do not. Since also the respective MTSL (S-(1-oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)methyl methanesulfonothioate) labelled peptides fail to aggregate, molecular crowding due to the label, rather than the helix-inducing properties of TOAC, seems to be responsible. Following in situ oligomer formation of T0EZ by the change in rotational correlation time, two oligomers are observed, a 5-6 mer and a 15-18 mer. The EPR approach, particularly 95 GHz EPR, enables following oligomerization of one monomer at a time, suggesting that the cw-EPR approach presented is a novel tool to follow amyloid oligomerization with high resolution.

Erratum: First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector [Phys. Rev. Lett. 121, 051301 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

Remifentanil patient-controlled analgesia in labour: six-year audit of outcome data of the RemiPCA SAFE Network (2010-2015).

BACKGROUND: The RemiPCA SAFE Network was established to set standards and monitor maternal and neonatal outcomes when using remifentanil for labour analgesia. The aim of this analysis was to describe the development of the network standard and to report maternal and neonatal outcome data, including severe adverse events. METHODS: Data sets of the RemiPCA SAFE Network database from the initial six consecutive years (2010-2015) were retrospectively analysed. The data were analysed on an annual basis and set in context with changes of the network standard, i.e. adaptations of the network's standard operating procedure. Main outcomes reported are maternal and neonatal data regarding effectiveness and safety, such as satisfaction, need for bag/mask ventilation and/or cardiopulmonary resuscitation. RESULTS: Among 5740 data sets, no need for maternal ventilation or cardiopulmonary resuscitation was registered. Neonatal cardiopulmonary resuscitations, potentially related to remifentanil, occurred in 0.3%. In parallel with adaptations of the network standard, a moderate rate of maternal hypoxia (oxygen saturation <94% in 24.7%) was found, together with a low rate of supplemental oxygen requirement in neonates (5.0%). CONCLUSION: The RemiPCA SAFE Network data show that remifentanil patient-controlled analgesia can be applied safely. There is bias when data from real clinical settings are analysed retrospectively. Notwithstanding, the approach taken by the RemiPCA SAFE Network, with constant, systematic and standardised evaluation of multiple parameters during the course of labour, might identify trends and anomalies and guide the development and application of safety standards, when translating knowledge from scientific trials into clinical practice.

Manifestation of a solitary retinal astrocytic hamartoma in a patient with Best macular dystrophy.

PURPOSE: To report the case of an adolescent male with a history of Best macular dystrophy and retinal astrocytic hamartoma. OBSERVATIONS: A 15 year old male with a history of Best macular dystrophy who had been followed by ophthalmology for 9 years was noted to have progressive enlargement of a superonasal peripapillary retinal lesion. Imaging and exam are consistent with a diagnosis of retinal astrocytic hamartoma. There were no extraocular signs or symptoms that were diagnostic of a phakamatosis. Genetic testing was positive for a mutation in BEST1, but not TSC1 or TSC2. CONCLUSIONS AND IMPORTANCE: Retinal astrocytic hamartoma is an unusual association with Best macular dystrophy, and this case highlights the balanced approach needed to navigate a potentially complex work-up.