The experiences of new mothers accessing feeding support for infants with down syndrome during the COVID-19 pandemic.

Infants with Down syndrome are more likely to experience feeding problems and mothers are likely to require more feeding support than mothers of typically developing infants. During the COVID-19 pandemic, many feeding support services changed from face-to-face to online, which impacted some maternal feeding experiences negatively, but no studies to date have explored the impact for mothers of infants with Down syndrome. Thematic analysis was conducted on semi-structured interviews from thirteen new mothers of infants (aged 8-17 months) with Down syndrome in the UK. Three superordinate themes were generated: (1) Every baby with Down syndrome has a unique journey, (2) There's no point asking, they won't know, (3) Lack of in-person support. Many mothers expressed frustrations over health professionals' lack of Down syndrome specific knowledge resulting in unmet needs, further magnified due to the nature of the virtual support being offered. Moreover, mothers struggled with reduced social support from other mothers when encountering feeding problems. These results hold real-world implications for health professionals who could provide more specialised face-to-face feeding support to mothers of infants with Down syndrome. This should be prioritised for children's overall development and mothers' wellbeing.

Excited-Band Coherent Delocalization for Improved Optical Lattice Clock Performance.

We implement coherent delocalization as a tool for improving the two primary metrics of atomic clock performance: systematic uncertainty and instability. By decreasing atomic density with coherent delocalization, we suppress cold-collision shifts and two-body losses. Atom loss attributed to Landau-Zener tunneling in the ground lattice band would compromise coherent delocalization at low trap depths for our ^{171}Yb atoms; hence, we implement for the first time delocalization in excited lattice bands. Doing so increases the spatial distribution of atoms trapped in the vertically oriented optical lattice by ∼7 times. At the same time, we observe a reduction of the cold-collision shift by 6.5(8) times, while also making inelastic two-body loss negligible. With these advantages, we measure the trap-light-induced quenching rate and natural lifetime of the ^{3}P_{0} excited state as 5.7(7)×10^{-4} E_{r}^{-1} s^{-1} and 19(2) s, respectively.

Inclusivity for children with autism spectrum disorders: Parents' reflections of the school learning environment versus home learning during COVID-19.

Whilst attendance in mainstream school helps encourage inclusivity, these environments are recognised as being particularly challenging for young people with an autism spectrum disorder (ASD). The COVID-19 pandemic brought a novel transition as young people moved from school to home-learning. This study compared the experiences of parents of children with ASD and co-occurring health difficulties of school-learning environments with their home-learning environments during COVID-19 lockdown. An interpretative phenomenological analysis was conducted on semi-structured interviews from six parents of children (aged 8-15 years old) with ASD. Four superordinate themes were generated: Interactions between Health, ASD and Learning Environments; School Support and Managing Health Needs; Seeking Solutions; and Learning from COVID-19 Lockdown. The study highlighted the impact of ASD and co-occurring health difficulties on learning where parents found ways to provide positive home-learning environments which could be used and/or transferred back into school environments. These results hold real-world implications where educators could treat sensory and ASD friendly environments as standard and include genuine adjustments for children with ASD and additional needs. A flexible home-learning approach using parental knowledge around environmental adjustments that support learning, wellbeing and a sense of inclusion should be prioritised for children's overall development and wellbeing in these unprecedented times, and beyond.

Subrecoil Clock-Transition Laser Cooling Enabling Shallow Optical Lattice Clocks.

Laser cooling is a key ingredient for quantum control of atomic systems in a variety of settings. In divalent atoms, two-stage Doppler cooling is typically used to bring atoms to the µK regime. Here, we implement a pulsed radial cooling scheme using the ultranarrow ^{1}S_{0}-^{3}P_{0} clock transition in ytterbium to realize subrecoil temperatures, down to tens of nK. Together with sideband cooling along the one-dimensional lattice axis, we efficiently prepare atoms in shallow lattices at an energy of 6 lattice recoils. Under these conditions key limits on lattice clock accuracy and instability are reduced, opening the door to dramatic improvements. Furthermore, tunneling shifts in the shallow lattice do not compromise clock accuracy at the 10^{-19} level.

Emotion production of facial expressions: A comparison of deaf and hearing children.

The production of facial expressions is an important skill that allows children to share and adapt emotions during social interactions. While deaf children are reported to show delays in their social and emotion understanding, the way in which they produce facial expressions of emotions has been relatively unexplored. The present study investigated the production of facial expressions of emotions by young congenitally deaf children. Six facial expressions of emotions produced by 5 congenitally deaf children and 5 hearing children (control group) were filmed across three tasks: 1) voluntarily posed expression of emotion 2) responding to social stories 3) intentionally mimicking expressions of emotion. The recorded videos were analysed using a software based of the Facial Action Coding System (FACS), and then judged by adult raters using two different scales: according to the emotion elicited (i.e. accuracy) and the intensity of the emotion produced. The results of both measurement scales showed that all children (deaf and hearing) were able to produce socially recognisable prototypical configuration of facial expressions. However, the deaf children were rated by adults as expressing their emotions with greater intensity compared to the hearing children. The results suggest deaf children may show more exaggerated facial expressions of emotion, possibly to avoid any ambiguity in communication.

The possible use of precision tinted lenses to improve social cognition in children with autism spectrum disorders.

A masked randomised control design compared the effectiveness of precision ophthalmic tints in improving the recognition of emotion in Autism Spectrum Disorders (ASD). Fourteen children aged 10-14 with ASD and 14 control children matched on verbal and non-verbal IQ, wore spectacles with coloured lenses to complete two tasks that involved the observation of coloured video sequences in which social interactions were depicted. On one occasion (randomly first or second) the coloured lenses provided light of a colour that the child had one month previously selected as optimal for the clarity of text. On the other occasion the lenses differed in CIE UCS chromaticity by 0.077. Performance in the ASD group was superior in both social interaction tasks with the lenses that provided the optimal colour of light.

New bounds on dark matter coupling from a global network of optical atomic clocks.

We report on the first Earth-scale quantum sensor network based on optical atomic clocks aimed at dark matter (DM) detection. Exploiting differences in the susceptibilities to the fine-structure constant of essential parts of an optical atomic clock, i.e., the cold atoms and the optical reference cavity, we can perform sensitive searches for DM signatures without the need for real-time comparisons of the clocks. We report a two orders of magnitude improvement in constraints on transient variations of the fine-structure constant, which considerably improves the detection limit for the standard model (SM)-DM coupling. We use Yb and Sr optical atomic clocks at four laboratories on three continents to search for both topological defect and massive scalar field candidates. No signal consistent with a DM coupling is identified, leading to considerably improved constraints on the DM-SM couplings.

Atomic clock performance enabling geodesy below the centimetre level.

The passage of time is tracked by counting oscillations of a frequency reference, such as Earth's revolutions or swings of a pendulum. By referencing atomic transitions, frequency (and thus time) can be measured more precisely than any other physical quantity, with the current generation of optical atomic clocks reporting fractional performance below the 10-17 level1-5. However, the theory of relativity prescribes that the passage of time is not absolute, but is affected by an observer's reference frame. Consequently, clock measurements exhibit sensitivity to relative velocity, acceleration and gravity potential. Here we demonstrate local optical clock measurements that surpass the current ability to account for the gravitational distortion of space-time across the surface of Earth. In two independent ytterbium optical lattice clocks, we demonstrate unprecedented values of three fundamental benchmarks of clock performance. In units of the clock frequency, we report systematic uncertainty of 1.4 × 10-18, measurement instability of 3.2 × 10-19 and reproducibility characterized by ten blinded frequency comparisons, yielding a frequency difference of [-7 ± (5)stat ± (8)sys] × 10-19, where 'stat' and 'sys' indicate statistical and systematic uncertainty, respectively. Although sensitivity to differences in gravity potential could degrade the performance of the clocks as terrestrial standards of time, this same sensitivity can be used as a very sensitive probe of geopotential5-9. Near the surface of Earth, clock comparisons at the 1 × 10-18 level provide a resolution of one centimetre along the direction of gravity, so the performance of these clocks should enable geodesy beyond the state-of-the-art level. These optical clocks could further be used to explore geophysical phenomena10, detect gravitational waves11, test general relativity12 and search for dark matter13-17.

Faraday-Shielded dc Stark-Shift-Free Optical Lattice Clock.

We demonstrate the absence of a dc Stark shift in an ytterbium optical lattice clock. Stray electric fields are suppressed through the introduction of an in-vacuum Faraday shield. Still, the effectiveness of the shielding must be experimentally assessed. Such diagnostics are accomplished by applying high voltage to six electrodes, which are grounded in normal operation to form part of the Faraday shield. Our measurements place a constraint on the dc Stark shift at the 10^{-20} level, in units of the clock frequency. Moreover, we discuss a potential source of error in strategies to precisely measure or cancel nonzero dc Stark shifts, attributed to field gradients coupled with the finite spatial extent of the lattice-trapped atoms. With this consideration, we find that Faraday shielding, complemented with experimental validation, provides both a practically appealing and effective solution to the problem of dc Stark shifts in optical lattice clocks.

Compact, thermal-noise-limited reference cavity for ultra-low-noise microwave generation.

We demonstrate an easy-to-manufacture 25-mm-long ultra-stable optical reference cavity for transportable photonic microwave generation systems. Employing a rigid holding geometry that is first-order insensitive to the squeezing force and a cavity geometry that improves the thermal noise limit at room temperature, we observe a laser phase noise that is nearly thermal noise limited for three frequency decades (1 Hz to 1 kHz offset) and supports 10 GHz generation with phase noise near -100 dBc/Hz at 1 Hz offset and <-173 dBc/Hz for all offsets >600 Hz. The fractional frequency stability reaches 2×10-15 at 0.1 s of averaging.

Hyperpolarizability and Operational Magic Wavelength in an Optical Lattice Clock.

Optical clocks benefit from tight atomic confinement enabling extended interrogation times as well as Doppler- and recoil-free operation. However, these benefits come at the cost of frequency shifts that, if not properly controlled, may degrade clock accuracy. Numerous theoretical studies have predicted optical lattice clock frequency shifts that scale nonlinearly with trap depth. To experimentally observe and constrain these shifts in an ^{171}Yb optical lattice clock, we construct a lattice enhancement cavity that exaggerates the light shifts. We observe an atomic temperature that is proportional to the optical trap depth, fundamentally altering the scaling of trap-induced light shifts and simplifying their parametrization. We identify an "operational" magic wavelength where frequency shifts are insensitive to changes in trap depth. These measurements and scaling analysis constitute an essential systematic characterization for clock operation at the 10^{-18} level and beyond.

Telomerase reverse transcriptase expression protects transformed human cells against DNA-damaging agents, and increases tolerance to chromosomal instability.

Reactivation of telomerase reverse transcriptase (TERT) expression is found in more than 85% of human cancers. The remaining cancers rely on the alternative lengthening of telomeres (ALT), a recombination-based mechanism for telomere-length maintenance. Prevalence of TERT reactivation over the ALT mechanism was linked to secondary TERT function unrelated to telomere length maintenance. To characterize this non-canonical function, we created a panel of ALT cells with recombinant expression of TERT and TERT variants: TERT-positive ALT cells showed higher tolerance to genotoxic insults compared with their TERT-negative counterparts. We identified telomere synthesis-defective TERT variants that bestowed similar genotoxic stress tolerance, indicating that telomere synthesis activity is dispensable for this survival phenotype. TERT expression improved the kinetics of double-strand chromosome break repair and reduced DNA damage-related nuclear division abnormalities, a phenotype associated with ALT tumors. Despite this reduction in cytological abnormalities, surviving TERT-positive ALT cells were found to have gross chromosomal instabilities. We sorted TERT-positive cells with cytogenetic changes and followed their growth. We found that the chromosome-number changes persisted, and TERT-positive ALT cells surviving genotoxic events propagated through subsequent generations with new chromosome numbers. Our data confirm that telomerase expression protects against double-strand DNA (dsDNA)-damaging events, and show that this protective function is uncoupled from its role in telomere synthesis. TERT expression promotes oncogene-transformed cell growth by reducing the inhibitory effects of cell-intrinsic (telomere attrition) and cell-extrinsic (chemical- or metabolism-induced genotoxic stress) challenges. These data provide the impetus to develop new therapeutic interventions for telomerase-positive cancers through simultaneous targeting of multiple telomerase activities.

Differential KrasV12 protein levels control a switch regulating lung cancer cell morphology and motility.

INTRODUCTION: Oncogenic Kras mutations are important drivers of lung cancer development and metastasis. They are known to activate numerous cellular signaling pathways implicated in enhanced proliferation, survival, tumorigenicity and motility during malignant progression. OBJECTIVES: Most previous studies of Kras in cancer have focused on the comparison of cell states in the absence or presence of oncogenic Kras mutations. Here we show that differential expression of the constitutively active mutation KrasV12 has profound effects on cell morphology and motility that drive metastatic processes. METHODS: The study relies on lung cancer cell transformation models, patient-derived lung cancer cell lines, and human lung tumor sections combined with molecular biology techniques, live-cell imaging and staining methods. RESULTS: Our analysis shows two cell functional states driven by KrasV12 protein levels: a non-motile state associated with high KrasV12 levels and tumorigenicity, and a motile state associated with low KrasV12 levels and cell dissemination. Conversion between the states is conferred by differential activation of a mechano-sensitive double-negative feedback between KrasV12/ERK/Myosin II and matrix-adhesion signaling. KrasV12 expression levels change upon cues such as hypoxia and integrin-mediated cell-matrix adhesion, rendering KrasV12 levels an integrator of micro-environmental signals that translate into cellular function. By live cell imaging of tumor models we observe shedding of mixed high and low KrasV12 expressers forming multi-functional collectives with potentially optimal metastatic properties composed of a highly mobile and a highly tumorigenic unit. DISCUSSION: Together these data highlight previously unappreciated roles for the quantitative effects of expression level variation of oncogenic signaling molecules in conferring fundamental alterations in cell function regulation required for cancer progression.

Atomic clock with 1×10(-18) room-temperature blackbody Stark uncertainty.

The Stark shift due to blackbody radiation (BBR) is the key factor limiting the performance of many atomic frequency standards, with the BBR environment inside the clock apparatus being difficult to characterize at a high level of precision. Here we demonstrate an in-vacuum radiation shield that furnishes a uniform, well-characterized BBR environment for the atoms in an ytterbium optical lattice clock. Operated at room temperature, this shield enables specification of the BBR environment to a corresponding fractional clock uncertainty contribution of 5.5×10(-19). Combined with uncertainty in the atomic response, the total uncertainty of the BBR Stark shift is now 1×10(-18). Further operation of the shield at elevated temperatures enables a direct measure of the BBR shift temperature dependence and demonstrates consistency between our evaluated BBR environment and the expected atomic response.

An atomic clock with 10(-18) instability.

Atomic clocks have been instrumental in science and technology, leading to innovations such as global positioning, advanced communications, and tests of fundamental constant variation. Timekeeping precision at 1 part in 10(18) enables new timing applications in relativistic geodesy, enhanced Earth- and space-based navigation and telescopy, and new tests of physics beyond the standard model. Here, we describe the development and operation of two optical lattice clocks, both using spin-polarized, ultracold atomic ytterbium. A measurement comparing these systems demonstrates an unprecedented atomic clock instability of 1.6 × 10(-18) after only 7 hours of averaging.

High-accuracy measurement of atomic polarizability in an optical lattice clock.

Presently, the Stark effect contributes the largest source of uncertainty in a ytterbium optical atomic clock through blackbody radiation. By employing an ultracold, trapped atomic ensemble and high stability optical clock, we characterize the quadratic Stark effect with unprecedented precision. We report the ytterbium optical clock's sensitivity to electric fields (such as blackbody radiation) as the differential static polarizability of the ground and excited clock levels α(clock) = 36.2612(7) kHz (kV/cm)(-2). The clock's uncertainty due to room temperature blackbody radiation is reduced by an order of magnitude to 3×10(-17).

p-Wave cold collisions in an optical lattice clock.

We study ultracold collisions in fermionic ytterbium by precisely measuring the energy shifts they impart on the atoms' internal clock states. Exploiting Fermi statistics, we uncover p-wave collisions, in both weakly and strongly interacting regimes. With the higher density afforded by two-dimensional lattice confinement, we demonstrate that strong interactions can lead to a novel suppression of this collision shift. In addition to reducing the systematic errors of lattice clocks, this work has application to quantum information and quantum simulation with alkaline-earth atoms.

ACTN3 genotype does not influence muscle power.

The R577X polymorphism within the ACTN3 gene has been associated with elite athletic performance, strength, power, fat free mass, and adaptations to strength training, though inconsistencies exist in the literature. The specific muscle power phenotypes most influenced by the polymorphism are uncertain. The purpose of this study was to examine the association between ACTN3 R577X genotype and muscle power phenotypes. Recreationally active young men and women (N=57) were selected to complete 2 muscle performance assessments, an isokinetic fatigue protocol at testing speeds of 180° s (-1) and 250° s (-1) and a 30 s Wingate test. Isokinetic torque and Wingate power significantly decreased over the duration of each test, but no differences in the rate of decline were observed among ACTN3 genotype groups. Similarly, no significant genotype differences were observed for isokinetic peak torque, Wingate absolute or relative peak power, or fatigue index. These results indicate that in recreationally active individuals the ACTN3 R577X polymorphism is not associated with muscle performance phenotypes, supporting recent findings that R577X may only be important for predicting performance in elite athletes. Our data also indicate that using this polymorphism for genetic screening in the lay population is scientifically questionable.

Spin-1/2 optical lattice clock.

We experimentally investigate an optical clock based on ;{171}Yb (I = 1/2) atoms confined in an optical lattice. We have evaluated all known frequency shifts to the clock transition, including a density-dependent collision shift, with a fractional uncertainty of 3.4 x 10;{-16}, limited principally by uncertainty in the blackbody radiation Stark shift. We measured the absolute clock transition frequency relative to the NIST-F1 Cs fountain clock and find the frequency to be 518 295 836 590 865.2(0.7) Hz.

Probing interactions between ultracold fermions.

At ultracold temperatures, the Pauli exclusion principle suppresses collisions between identical fermions. This has motivated the development of atomic clocks with fermionic isotopes. However, by probing an optical clock transition with thousands of lattice-confined, ultracold fermionic strontium atoms, we observed density-dependent collisional frequency shifts. These collision effects were measured systematically and are supported by a theoretical description attributing them to inhomogeneities in the probe excitation process that render the atoms distinguishable. This work also yields insights for zeroing the clock density shift.