Resolving the gravitational redshift across a millimetre-scale atomic sample.

Einstein's theory of general relativity states that clocks at different gravitational potentials tick at different rates relative to lab coordinates-an effect known as the gravitational redshift1. As fundamental probes of space and time, atomic clocks have long served to test this prediction at distance scales from 30 centimetres to thousands of kilometres2-4. Ultimately, clocks will enable the study of the union of general relativity and quantum mechanics once they become sensitive to the finite wavefunction of quantum objects oscillating in curved space-time. Towards this regime, we measure a linear frequency gradient consistent with the gravitational redshift within a single millimetre-scale sample of ultracold strontium. Our result is enabled by improving the fractional frequency measurement uncertainty by more than a factor of 10, now reaching 7.6 × 10-21. This heralds a new regime of clock operation necessitating intra-sample corrections for gravitational perturbations.

Experiences of families post treatment for childhood brain tumours during medical clinic consultations regarding health-related quality of life, unmet needs and communication barriers: A qualitative exploration.

BACKGROUND: Many studies highlight poor health-related quality of life (HRQoL) in children treated for brain tumours and their parents. However, little is known about the extent to which their informational, healthcare and communication needs regarding HRQoL are met during medical outpatient consultations. AIM: To explore the experiences of families regarding communication with physicians about HRQoL issues during consultations after treatment for childhood brain tumours. METHODS: Interviews were conducted with 18 families of children and adolescents aged 8-17 years after completion of brain tumour treatment. Participants had completed treatment within the last 5 years and were receiving regular outpatient follow-up care. Thematic analysis was undertaken using the Framework Method. RESULTS: Five main themes were identified: (i) unmet emotional and mental health needs; (ii) double protection; (iii) unmet information needs; (iv) communication barriers within consultations; and (v) finding a new normal. CONCLUSION: There was a need to improve communication between clinicians and these families, improve information provision, and overcome barriers to conversing with children within these outpatient consultations. Children and their parents should be supported to voice their current needs and concerns regarding their HRQoL. These findings will inform further development of the UK version of the 'KLIK' patient- and parent-reported outcome (PROM) portal.

Transatlantic progress in measurement of cognitive outcomes in paediatric oncology trials.

The importance of measuring quality of survival within paediatric oncology trials is increasingly recognised. However, capturing neuropsychological outcomes and other aspects of quality of survival in the context of large or multinational trials can be challenging. We provide examples of protocols designed to address this challenge recently employed in clinical trials in the USA and Europe. We discuss their respective strengths and challenges, obstacles encountered and future opportunities for transatlantic collaboration.

Preparation of the Spin-Mott State: A Spinful Mott Insulator of Repulsively Bound Pairs.

We observe and study a special ground state of bosons with two spin states in an optical lattice: the spin-Mott insulator, a state that consists of repulsively bound pairs that is insulating for both spin and charge transport. Because of the pairing gap created by the interaction anisotropy, it can be prepared with low entropy and can serve as a starting point for adiabatic state preparation. We find that the stability of the spin-Mott state depends on the pairing energy, and observe two qualitatively different decay regimes, one of which exhibits protection by the gap.

Precision Metrology Meets Cosmology: Improved Constraints on Ultralight Dark Matter from Atom-Cavity Frequency Comparisons.

We conduct frequency comparisons between a state-of-the-art strontium optical lattice clock, a cryogenic crystalline silicon cavity, and a hydrogen maser to set new bounds on the coupling of ultralight dark matter to standard model particles and fields in the mass range of 10^{-16}-10^{-21} eV. The key advantage of this two-part ratio comparison is the differential sensitivity to time variation of both the fine-structure constant and the electron mass, achieving a substantially improved limit on the moduli of ultralight dark matter, particularly at higher masses than typical atomic spectroscopic results. Furthermore, we demonstrate an extension of the search range to even higher masses by use of dynamical decoupling techniques. These results highlight the importance of using the best-performing atomic clocks for fundamental physics applications, as all-optical timescales are increasingly integrated with, and will eventually supplant, existing microwave timescales.

Peer Relationship Experiences Of Deaf And Hard-Of-Hearing Adolescents.

Deaf and hard-of-hearing adolescents (DHH) experience more peer problems and lower levels of friendships than their hearing peers. This study used a qualitative approach to identify their experiences of peer problems and factors influencing them. A sample of 30, 13-19 year-old DHH adolescents with a moderate to profound hearing loss, drawn from a population-based cohort study in which their receptive language and social-emotional skills had been assessed, underwent semi-structured interviews. Interviews were analyzed using thematic analysis. Participants reported that, overall, they had developed positive and rewarding relationships with their peers, notwithstanding their earlier experience of being bullied. Conflicts and infrequency of interaction in their friendships were mainly reported by girls. Adolescents with moderate hearing loss were identified as facing the same or even more barriers than adolescents with severe to profound hearing loss in making new friends. Implications for educational practice are discussed.

Demonstration of a Timescale Based on a Stable Optical Carrier.

We report on the first timescale based entirely on optical technology. Existing timescales, including those incorporating optical frequency standards, rely exclusively on microwave local oscillators owing to the lack of an optical oscillator with the required frequency predictability and stability for reliable steering. We combine a cryogenic silicon cavity exhibiting improved long-term stability and an accurate ^{87}Sr lattice clock to form a timescale that outperforms them all. Our timescale accumulates an estimated time error of only 48±94 ps over 34 days of operation. Our analysis indicates that this timescale is capable of reaching a stability below 1×10^{-17} after a few months of averaging, making timekeeping at the 10^{-18} level a realistic prospect.

The underlying etiology of infantile spasms (West syndrome): Information from the International Collaborative Infantile Spasms Study (ICISS).

OBJECTIVE: To determine the underlying etiologies in a contemporary cohort of infants with infantile spasms and to examine response to treatment. METHODS: Identification of the underlying etiology and response to treatment in 377 infants enrolled in a clinical trial of the treatment of infantile spasms between 2007 and 2014 using a systematic review of history, examination, and investigations. They were classified using the pediatric adaptation of International Classification of Diseases, Tenth Revision (ICD-10). RESULTS: A total of 219 of 377 (58%) had a proven etiology, of whom 128 (58%) responded, 58 of 108 (54%) were allocated hormonal treatment, and 70 of 111 (63%) had combination therapy. Fourteen of 17 (82%, 95% confidence interval [CI] 59% to 94%) infants with stroke and infarct responded (compared to 114 of 202 for the rest of the proven etiology group (56%, 95% CI 48% to 62%, chi-square 4.3, P = .037): the better response remains when treatment allocation and lead time are taken into account (odds ratio 5.1, 95% CI 1.1 to 23.6, P = .037). Twenty of 37 (54%, 95% CI 38% to 70%) infants with Down syndrome had cessation of spasms compared to 108 of 182 (59%, 95% CI 52% to 66%, chi-square 0.35, P = .55) for the rest of the proven etiology group. The lack of a significant difference remains after taking treatment modality and lead-time into account (odds ratio 0.8, 95% CI 0.4 to 1.7, P = .62). In Down syndrome infants, treatment modality did not appear to affect response: 11 of 20 (55%) allocated hormonal therapy responded, compared to 9 of 17 (53%) allocated combination therapy. SIGNIFICANCE: This classification allows easy comparison with other classifications and with our earlier reports. Stroke and infarct have a better outcome than other etiologies, whereas Down syndrome might not respond to the addition of vigabatrin to hormonal treatment.

Radiographic Soft Tissue Thickness Differentiating Pyogenic Flexor Tenosynovitis From Other Finger Infections.

PURPOSE: Characteristic swelling has been described as a differentiating sign of pyogenic flexor tenosynovitis (PFT) but has not been validated. We conducted a retrospective study of adults with finger infections to compare radiographic parameters of soft tissue dimensions. Our hypothesis was that in patients with digit infections, radiographic soft tissue thickness measurement would differ between PFT and non-PFT infected digits. METHODS: Patients with a finger infection and radiographic evaluation were identified retrospectively at a large academic medical center and divided into 2 groups: PFT (n = 31) and non-PFT infections (n = 31). We defined PFT as purulence in the tendon sheath or positive culture growth from the sheath at surgery. Non-PFT infections included all other finger infections such as abscesses and cellulitis. A total of 15 radiographic measurements were made on all included digits. Ratios and differences were calculated to characterize the pattern of swelling for each infected finger. Bivariate analysis was performed to identify potential predictor variables between the PFT and non-PFT groups. Logistic regression was performed to reduce confounding and model potential relationships. RESULTS: Neither presence of diffuse swelling nor the shape of finger swelling distinguished PFT from non-PFT infections. All finger infections resulted in diffuse swelling. Pyogenic flexor tenosynovitis was distinguished by differential volar soft tissue thickness minus dorsal soft tissue thickness on radiographs at the proximal phalanx level (9 ± 1 mm for PFT vs 5 ± 1 mm for non-PFT). This was an independent predictor of PFT. The area under the receiver operating curve was 0.83 (95% confidence interval, 0.73-0.94). A difference between volar and dorsal soft tissue swelling of 7 mm or greater had a positive predictive value of 82% with a sensitivity of 84% and specificity of 74%. A difference of 10 mm predicted PFT infection with 76% probability (95% confidence interval, 73% to 99%). CONCLUSIONS: Pyogenic flexor tenosynovitis may result in uniform finger swelling, but this does not appear to distinguish PFT from other finger infections. Acute PFT swelling is distinguished by differential volar versus dorsal radiographic soft tissue thickness at the level of the proximal phalanx. The term "fusiform swelling" is a misnomer for the appearance of acute PFT because the finger is not spindle-shaped. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic IV.

Language and reading comprehension in middle childhood predicts emotional and behaviour difficulties in adolescence for those with permanent childhood hearing loss.

BACKGROUND: Permanent childhood hearing loss (PCHL) is associated with an elevated level of emotional and behaviour difficulties (EBD). In children and adolescents with PCHL, EBD has been found to be linked to language ability in children with PCHL. The present study was designed to test whether childhood language and/or reading comprehension abilities of children with PCHL predict subsequent EBD in adolescence. METHODS: Language comprehension (LC) and reading comprehension (RC) were measured at ages 6-10 years (Time 1) and 13-20 years (Time 2) in participants with PCHL who preferred to communicate using spoken language (n = 57) and a hearing comparison group (n = 38). EBD was measured at both time points by parent and by teacher ratings on the Strengths and Difficulties Questionnaire. RESULTS: Within the PCHL group there were negative correlations between EBD scores and concurrent LC and RC scores at Time 1 and at Time 2. Cross-lagged latent variable models fitted to the longitudinal data indicated that the associations between LC, RC and teacher-rated EBD were more likely to arise from the impact of LC and RC on behaviour rather than the other way around. CONCLUSIONS: In those with PCHL, poor language and reading comprehension in middle childhood increased the risk of emotional and behaviour difficulties at school in the teenage years. The results suggest that effective language and literacy interventions for children with hearing loss may also bring benefits to their mental health.

Phonological processing during silent reading in teenagers who are deaf/hard of hearing: an eye movement investigation.

There has been considerable variability within the literature concerning the extent to which deaf/hard of hearing individuals are able to process phonological codes during reading. Two experiments are reported in which participants' eye movements were recorded as they read sentences containing correctly spelled words (e.g., church), pseudohomophones (e.g., cherch), and spelling controls (e.g., charch). We examined both foveal processing and parafoveal pre-processing of phonology for three participant groups-teenagers with permanent childhood hearing loss (PCHL), chronological age-matched controls, and reading age-matched controls. The teenagers with PCHL showed a pseudohomophone advantage from both directly fixated words and parafoveal preview, similar to their hearing peers. These data provide strong evidence for phonological recoding during silent reading in teenagers with PCHL.

A Strategy for Changing Adherence to National Guidelines for Decreasing Laboratory Testing for Early Breast Cancer Patients.

INTRODUCTION: Past studies indicate delays in adoption of consensus-based guideline updates. In June 2016, the National Comprehensive Cancer Network changed its guidelines from routine testing to omission of ordering complete blood cell count (CBC) and liver function tests (LFT) in patients with early breast cancer. In response, we developed an implementation strategy to discontinue our historical practice of routine ordering of these tests in asymptomatic patients. METHODS: The ordering of CBC and LFT for clinical stage I-IIIA breast cancer patients was audited in 2016. In June 2016, we utilized the levers of the National Quality Strategy implementation methodology to enact a system-wide change to omit routine ordering. To measure the plan's effectiveness, guideline compliance for ordering was tracked continually. RESULTS: Of 92 patients with early stage cancer in 2016, the overall rate of compliance with guidelines for ordering a CBC and LFT was 82% (88/107) and 87% (93/107), respectively. Segregated by the pre- and post-guideline change time period, the compliance rates for ordering a CBC and LFT were 78% and 87% (P = 0.076). CONCLUSION: In contrast to historical reports of delays in adoption of new evidence-based guideline changes, we were able to quickly change provider practice during the transition from routine ordering to omission of ordering screening blood tests in newly diagnosed patients with early breast cancer.

Language Outcomes in Deaf or Hard of Hearing Teenagers Who Are Spoken Language Users: Effects of Universal Newborn Hearing Screening and Early Confirmation.

OBJECTIVES: This study aimed to examine whether (a) exposure to universal newborn hearing screening (UNHS) and b) early confirmation of hearing loss were associated with benefits to expressive and receptive language outcomes in the teenage years for a cohort of spoken language users. It also aimed to determine whether either of these two variables was associated with benefits to relative language gain from middle childhood to adolescence within this cohort. DESIGN: The participants were drawn from a prospective cohort study of a population sample of children with bilateral permanent childhood hearing loss, who varied in their exposure to UNHS and who had previously had their language skills assessed at 6-10 years. Sixty deaf or hard of hearing teenagers who were spoken language users and a comparison group of 38 teenagers with normal hearing completed standardized measures of their receptive and expressive language ability at 13-19 years. RESULTS: Teenagers exposed to UNHS did not show significantly better expressive (adjusted mean difference, 0.40; 95% confidence interval [CI], -0.26 to 1.05; d = 0.32) or receptive (adjusted mean difference, 0.68; 95% CI, -0.56 to 1.93; d = 0.28) language skills than those who were not. Those who had their hearing loss confirmed by 9 months of age did not show significantly better expressive (adjusted mean difference, 0.43; 95% CI, -0.20 to 1.05; d = 0.35) or receptive (adjusted mean difference, 0.95; 95% CI, -0.22 to 2.11; d = 0.42) language skills than those who had it confirmed later. In all cases, effect sizes were of small size and in favor of those exposed to UNHS or confirmed by 9 months. Subgroup analysis indicated larger beneficial effects of early confirmation for those deaf or hard of hearing teenagers without cochlear implants (N = 48; 80% of the sample), and these benefits were significant in the case of receptive language outcomes (adjusted mean difference, 1.55; 95% CI, 0.38 to 2.71; d = 0.78). Exposure to UNHS did not account for significant unique variance in any of the three language scores at 13-19 years beyond that accounted for by existing language scores at 6-10 years. Early confirmation accounted for significant unique variance in the expressive language information score at 13-19 years after adjusting for the corresponding score at 6-10 years (R change = 0.08, p = 0.03). CONCLUSIONS: This study found that while adolescent language scores were higher for deaf or hard of hearing teenagers exposed to UNHS and those who had their hearing loss confirmed by 9 months, these group differences were not significant within the whole sample. There was some evidence of a beneficial effect of early confirmation of hearing loss on relative expressive language gain from childhood to adolescence. Further examination of the effect of these variables on adolescent language outcomes in other cohorts would be valuable.

Coherence Times of Bose-Einstein Condensates beyond the Shot-Noise Limit via Superfluid Shielding.

We demonstrate a new way to extend the coherence time of separated Bose-Einstein condensates that involves immersion into a superfluid bath. When both the system and the bath have similar scattering lengths, immersion in a superfluid bath cancels out inhomogeneous potentials either imposed by external fields or inherent in density fluctuations due to atomic shot noise. This effect, which we call superfluid shielding, allows for coherence lifetimes beyond the projection noise limit. We probe the coherence between separated condensates in different sites of an optical lattice by monitoring the contrast and decay of Bloch oscillations. Our technique demonstrates a new way that interactions can improve the performance of quantum devices.

Modified Constraint-Induced Movement Therapy as a Home-Based Intervention for Children With Cerebral Palsy.

PURPOSE: This study was designed to investigate the benefit to upper limb function of a home-based version of pediatric constraint-induced movement therapy, which was delivered across 2 months. METHODS: Nine children (mean age: 6 years, 9 months) with hemiplegic cerebral palsy participated in this A1-B-C-A2 design, where A1 and A2 were nonintervention phases. In phases B and C, participants wore a splint on the unaffected hand. In phase C, motivating feedback through a computer game was added. RESULTS: The Melbourne Assessment of Unilateral Upper Limb Function and the Quality of Upper Extremity Skills Test scores were significantly higher at the end of phases B (P = .037 and P = .006, respectively) and C (P = .001 and P = .001, respectively). Melbourne scores remained higher at the end of phase A2 (P = .001). CONCLUSIONS: A nonintensive form of home-based constraint-induced movement therapy was found to be effective. Improvements were larger after the second month of intervention.

Weyl Points in Three-Dimensional Optical Lattices: Synthetic Magnetic Monopoles in Momentum Space.

We show that a Hamiltonian with Weyl points can be realized for ultracold atoms using laser-assisted tunneling in three-dimensional optical lattices. Weyl points are synthetic magnetic monopoles that exhibit a robust, three-dimensional linear dispersion, identical to the energy-momentum relation for relativistic Weyl fermions, which are not yet discovered in particle physics. Weyl semimetals are a promising new avenue in condensed matter physics due to their unusual properties such as the topologically protected "Fermi arc" surface states. However, experiments on Weyl points are highly elusive. We show that this elusive goal is well within experimental reach with an extension of techniques recently used in ultracold gases.

Emotional and behavioural difficulties in children and adolescents with hearing impairment: a systematic review and meta-analysis.

The aim of this study is to estimate the extent to which children and adolescents with hearing impairment (HI) show higher rates of emotional and behavioural difficulties compared to normally hearing children. Studies of emotional and behavioural difficulties in children and adolescents were traced from computerized systematic searches supplemented, where appropriate, by studies referenced in previous narrative reviews. Effect sizes (Hedges' g) were calculated for all studies. Meta-analyses were conducted on the weighted effect sizes obtained for studies adopting the Strength and Difficulties Questionnaire (SDQ) and on the unweighted effect sizes for non-SDQ studies. 33 non-SDQ studies were identified in which emotional and behavioural difficulties in children with HI could be compared to normally hearing children. The unweighted average g for these studies was 0.36. The meta-analysis of the 12 SDQ studies gave estimated effect sizes of 0.23 (95% CI 0.07, 0.40), 0.34 (95% CI 0.19, 0.49) and -0.01 (95% CI -0.32, 0.13) for Parent, Teacher and Self-ratings of Total Difficulties, respectively. The SDQ sub-scale showing consistent differences across raters between groups with HI and those with normal hearing was Peer Problems. Children and adolescents with HI have scores on emotional and behavioural difficulties measures about a quarter to a third of a standard deviation higher than hearing children. Children and adolescents with HI are in need of support to help their social relationships particularly with their peers.

R-Ras is required for murine dendritic cell maturation and CD4+ T-cell priming.

R-Ras is a member of the RAS superfamily of small GTP-binding proteins. The physiologic function of R-Ras has not been fully elucidated. We found that R-Ras is expressed by lymphoid and nonlymphoid tissues and drastically up-regulated when bone marrow progenitors are induced to differentiate into dendritic cells (DCs). To address the role of R-Ras in DC functions, we generated a R-Ras-deficient mouse strain. We found that tumors induced in Rras(-/-) mice formed with shorter latency and attained greater tumor volumes. This finding has prompted the investigation of a role for R-Ras in the immune system. Indeed, Rras(-/-) mice were impaired in their ability to prime allogeneic and antigen-specific T-cell responses. Rras(-/-) DCs expressed lower levels of surface MHC class II and CD86 in response to lipopolysaccharide compared with wild-type DCs. This was correlated with a reduced phosphorylation of p38 and Akt. Consistently, R-Ras-GTP level was increased within 10 minutes of lipopolysaccharide stimulation. Furthermore, Rras(-/-) DCs have attenuated capacity to spread on fibronectin and form stable immunologic synapses with T cells. Altogether, these findings provide the first demonstration of a role for R-Ras in cell-mediated immunity and further expand on the complexity of small G-protein signaling in DCs.

CD43 in the nucleus and cytoplasm of lung cancer is a potential therapeutic target.

CD43 is a transmembrane sialoglycoprotein. Normally the molecule is only produced by white blood cells where it regulates functions such as intercellular adhesion, intracellular signaling, apoptosis, migration and proliferation. Two CD43 antibodies were used to interrogate 66 cases of non-small cell lung cancer (NSCLC) and 24 cases of small cell lung cancer (SCLC). In addition, we engineered the CD43-positive lung cancer cell line A549 to stably express either non-targeted or CD43-targeted small-interfering RNA (siRNA). These lines were then subjected to in vitro assays of apoptosis, natural killer (NK) cell cytotoxicity, intercellular adhesion and transendothelial migration. A xenograft mouse model evaluated the ability of the lines to grow primary tumors in vivo. CD43 was found to be expressed in the majority of both SCLC and NSCLC. Inclusive of CD43-negative tumors, differential patterns of nuclear and cytoplasmic expression of CD43 define four molecular subcategories of lung cancer. Targeting CD43 in A549 lung cancer cells, increased homotypic adhesion, decreased heterotypic adhesion and transendothelial migration, increased susceptibility to apoptosis and increased vulnerability to lysis by NK cells. Furthermore, targeting inhibited the growth of primary tumors in nude mice.