Comparing ultrastable lasers at 7 × 10-17 fractional frequency instability through a 2220 km optical fibre network.

Ultrastable lasers are essential tools in optical frequency metrology enabling unprecedented measurement precision that impacts on fields such as atomic timekeeping, tests of fundamental physics, and geodesy. To characterise an ultrastable laser it needs to be compared with a laser of similar performance, but a suitable system may not be available locally. Here, we report a comparison of two geographically separated lasers, over the longest ever reported metrological optical fibre link network, measuring 2220 km in length, at a state-of-the-art fractional-frequency instability of 7 × 10-17 for averaging times between 30 s and 200 s. The measurements also allow the short-term instability of the complete optical fibre link network to be directly observed without using a loop-back fibre. Based on the characterisation of the noise in the lasers and optical fibre link network over different timescales, we investigate the potential for disseminating ultrastable light to improve the performance of remote optical clocks.

Disinhibited attachment behavior among infants of mothers with borderline personality disorder, depression, and no diagnosis.

Disinhibited attachment behavior is related to early institutional rearing and to later social maladaptation. It is also seen among infants reared at home whose mothers have histories of child maltreatment or psychiatric hospitalization. However, little is known about the maternal psychiatric diagnoses that might be associated with disinhibited behavior or the mechanisms through which maternal diagnosis might influence infant behavior. In the current study (N = 59), 2 maternal diagnoses, borderline personality disorder (BPD; n = 13) and depression (n = 15), were compared with a no diagnosis group (n = 31) on extent of infant disinhibited behavior. Disinhibited infant behavior was assessed at infant age of 12-18 months using the validated Rating of Infant-Stranger Engagement. Mother-infant interaction was coded using the Atypical Maternal Behavior Instrument for Assessment and Classification. Results indicated that infants of mothers with BPD were significantly more likely to be rated as disinhibited in their behavior toward the stranger compared with infants of mothers with depression and with no diagnosis. Disinhibited behavior was further related to the quality of mother-infant interaction, and maternal frightened/disoriented interaction partially mediated the effect of maternal BPD on infant disinhibited behavior. Disinhibited behavior among previously institutionally reared infants is relatively resistant to intervention after toddlerhood and is associated with maladaptation into adolescence. Therefore, high priority should be placed on understanding the developmental trajectories of home-reared infants with disinhibited behavior and on providing early assessment and early parenting support to mothers with BPD. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Test of Special Relativity Using a Fiber Network of Optical Clocks.

Phase compensated optical fiber links enable high accuracy atomic clocks separated by thousands of kilometers to be compared with unprecedented statistical resolution. By searching for a daily variation of the frequency difference between four strontium optical lattice clocks in different locations throughout Europe connected by such links, we improve upon previous tests of time dilation predicted by special relativity. We obtain a constraint on the Robertson-Mansouri-Sexl parameter |α|≲1.1×10^{-8}, quantifying a violation of time dilation, thus improving by a factor of around 2 the best known constraint obtained with Ives-Stilwell type experiments, and by 2 orders of magnitude the best constraint obtained by comparing atomic clocks. This work is the first of a new generation of tests of fundamental physics using optical clocks and fiber links. As clocks improve, and as fiber links are routinely operated, we expect that the tests initiated in this Letter will improve by orders of magnitude in the near future.

Protocol for a multicentre, parallel-arm, 12-month, randomised, controlled trial of arthroscopic surgery versus conservative care for femoroacetabular impingement syndrome (FASHIoN).

INTRODUCTION: Femoroacetabular impingement (FAI) syndrome is a recognised cause of young adult hip pain. There has been a large increase in the number of patients undergoing arthroscopic surgery for FAI; however, a recent Cochrane review highlighted that there are no randomised controlled trials (RCTs) evaluating treatment effectiveness. We aim to compare the clinical and cost-effectiveness of arthroscopic surgery versus best conservative care for patients with FAI syndrome. METHODS: We will conduct a multicentre, pragmatic, assessor-blinded, two parallel arm, RCT comparing arthroscopic surgery to physiotherapy-led best conservative care. 24 hospitals treating NHS patients will recruit 344 patients over a 26-month recruitment period. Symptomatic adults with radiographic signs of FAI morphology who are considered suitable for arthroscopic surgery by their surgeon will be eligible. Patients will be excluded if they have radiographic evidence of osteoarthritis, previous significant hip pathology or previous shape changing surgery. Participants will be allocated in a ratio of 1:1 to receive arthroscopic surgery or conservative care. Recruitment will be monitored and supported by qualitative intervention to optimise informed consent and recruitment. The primary outcome will be pain and function assessed by the international hip outcome tool 33 (iHOT-33) measured 1-year following randomisation. Secondary outcomes include general health (short form 12), quality of life (EQ5D-5L) and patient satisfaction. The primary analysis will compare change in pain and function (iHOT-33) at 12 months between the treatment groups, on an intention-to-treat basis, presented as the mean difference between the trial groups with 95% CIs. The study is funded by the Health Technology Assessment Programme (13/103/02). ETHICS AND DISSEMINATION: Ethical approval is granted by the Edgbaston Research Ethics committee (14/WM/0124). The results will be disseminated through open access peer-reviewed publications, including Health Technology Assessment, and presented at relevant conferences. TRIAL REGISTRATION NUMBER: ISRCTN64081839; Pre-results.

The feasibility of conducting a randomised controlled trial comparing arthroscopic hip surgery to conservative care for patients with femoroacetabular impingement syndrome: the FASHIoN feasibility study.

To determine whether it was feasible to perform a randomized controlled trial (RCT) comparing arthroscopic hip surgery to conservative care in patients with femoroacetabular impingement (FAI). This study had two phases: a pre-pilot and pilot RCT. In the pre-pilot, we conducted interviews with clinicians who treated FAI and with FAI patients to determine their views about an RCT. We developed protocols for operative and conservative care. In the pilot RCT, we determined the rates of patient eligibility, recruitment and retention, to investigate the feasibility of the protocol and we established methods to assess treatment fidelity. In the pre-pilot phase, 32 clinicians were interviewed, of which 26 reported theoretical equipoise, but in example scenarios 7 failed to show clinical equipoise. Eighteen patients treated for FAI were also interviewed, the majority of whom felt that surgery and conservative care were acceptable treatments. Surgery was viewed by patients as a 'definitive solution'. Patients were motivated to participate in research but were uncomfortable about randomization. Randomization was more acceptable if the alternative was available at the end of the trial. In the pilot phase, 151 patients were assessed for eligibility. Sixty were eligible and invited to take part in the pilot RCT; 42 consented to randomization. Follow-up was 100% at 12 months. Assessments of treatment fidelity were satisfactory. An RCT to compare arthroscopic hip surgery with conservative care in patients with FAI is challenging but feasible. Recruitment has started for a full RCT.

The Relation between Severity of Autism and Caregiver-Child Interaction: a Study in the Context of Relationship Development Intervention.

The aim of this study was to examine the relations between severity of children's autism and qualities of parent-child interaction. We studied these variables at two points of time in children receiving a treatment that has a focus on social engagement, Relationship Development Intervention (RDI; Gutstein 2009). Participants were 18 parent-child dyads where the child (16 boys, 2 girls) had a diagnosis of autism and was between the ages of 2 and 12 years. The severity of the children's autism was assessed at baseline and later in treatment using the autism severity metric of the Autism Diagnostic Observation Schedule (ADOS; Gotham et al. Journal of Autism and Developmental Disorders, 39, 693-705 2009). Although the ADOS was designed as a diagnostic measure, ADOS calibrated severity scores (CSS) are increasingly used as one index of change (e.g., Locke et al. Autism, 18, 370-375 2014). Videotapes of parent-child interaction at baseline and later in treatment were rated by independent coders, for a) overall qualities of interpersonal relatedness using the Dyadic Coding Scales (DCS; Humber and Moss The American Journal of Orthopsychiatry, 75, 128-141 2005), and b) second-by-second parent-child Co-Regulation and Intersubjective Engagement (processes targeted by the treatment approach of RDI). Severity of autism was correlated with lower quality of parent-child interaction. Ratings on each of these variables changed over the course of treatment, and there was evidence that improvement was specifically related to the quality of parent-child interaction at baseline.

The effects of camicinal, a novel motilin agonist, on gastro-esophageal function in healthy humans-a randomized placebo controlled trial.

BACKGROUND: A proportion of patients with foregut dysmotility fail to respond to standard interventions. Motilin agonists may be beneficial in this group. We aimed to determine the effect of camicinal, a novel motilin agonist, on gastrointestinal physiology in healthy volunteers. METHODS: Healthy male subjects were randomly assigned to receive a single dose of 125 mg camicinal or placebo in a double-blind cross-over design. Esophageal function and reflux indices were assessed using high-resolution manometry (pre and 1.5-h post dose) and 24-h ambulatory multichannel intraluminal impedance/pH. After a standardized meal, subjects ingested a wireless motility capsule from which compartmental transit times and motility indices were derived. Subjects were restudied with the alternate intervention after 7 days. KEY RESULTS: The study subjects (12 male, mean age 47.4 years, range 22-55) tolerated the drug well, except one who exhibited mild abdominal pain on both placebo and camicinal. In comparison to placebo, gastric emptying time (GET) was accelerated following camicinal (-115.4 min, 95% confidence interval -194.4, -36.4, p = 0.009). No effect was demonstrable on esophageal function, small bowel, colonic, or whole bowel transit times and motility indices. With camicinal, as part of a post hoc analysis, there was a trend association between the percentage reduction in GET and total number of acidic reflux events (r = 0.56, p = 0.09). CONCLUSIONS & INFERENCES: Camicinal decreases GET and was generally well-tolerated. In health, the direct effects of camicinal are on accelerating GET with a potential secondary benefit of reducing reflux events, which warrant further exploration in patient cohorts.

Symbolizing as interpersonally grounded shifts in meaning: social play in children with and without autism.

The aim of this study was to examine the relation between symbolic play and communicative engagement among children with and without autism. Our predictions were firstly, that in moment-by-moment interactions during semi-structured interactive play with an adult, children with and without autism would tend to show shifts in meanings in symbolic play when engaged in coordinated states of joint engagement (events involving 'sharing-of-meaning'); secondly, that across atypically developing participants, sharing-of-meaning would (a) correlate with scores on a standardized test of pretend play, and (b) be inversely correlated with scores on the Autism Diagnostic Observation Schedule; and finally, that participants with autism would contrast with matched developmentally delayed participants in manifesting lower levels of joint engagement, lower levels of symbolic play, and fewer shifts in symbolic meaning. Each of these predictions was borne out. The intimate developmental relation between social engagement and symbolic play appears to be important for explaining the developmental psychopathology of autism.

Effectiveness of deep cleaning followed by hydrogen peroxide decontamination during high Clostridium difficile infection incidence.

BACKGROUND: Clostridium difficile infection (CDI) remains an infection control challenge, especially when environmental spore contamination and suboptimal cleaning may increase transmission risk. AIM: To substantiate the long-term effectiveness throughout a stroke rehabilitation unit (SRU) of deep cleaning and hydrogen peroxide decontamination (HPD), following a high incidence of CDI. METHODS: Extensive environmental sampling (342 sites on each occasion) for C. difficile using sponge wipes was performed: before and after deep cleaning with detergent/chlorine agent; immediately following HPD; and on two further occasions, 19 days and 20 weeks following HPD. C. difficile isolates underwent polymerase chain reaction ribotyping and multi-locus variable repeat analysis (MLVA). FINDINGS: C. difficile was recovered from 10.8%, 6.1%, 0.9%, 0% and 3.5% of sites at baseline, following deep cleaning, immediately after HPD, and 19 days and 20 weeks after HPD, respectively. C. difficile ribotypes recovered after deep cleaning matched those from CDI cases in the SRU during the previous 10 months. Similarly, 10/12 of the positive sites identified at 20 weeks post-HPD harboured the same C. difficile ribotype (002) and MLVA pattern as the isolate from the first post-HPD CDI case. CDI incidence [number of cases on SRU per 10 months (January-October 2011)] declined from 20 before to seven after the intervention. CONCLUSION: HPD, after deep cleaning with a detergent/chlorine agent, was highly effective for removing environmental C. difficile contamination. Long-term follow-up demonstrated that a CDI symptomatic patient can rapidly recontaminate the immediate environment. Determining a role for HPD should include long-term cost-effectiveness evaluations.

The coherence of autism.

There is a growing body of opinion that we should view autism as fractionable into different, largely independent sets of clinical features. The alternative view is that autism is a coherent syndrome in which principal features of the disorder stand in intimate developmental relationship with each other. Studies of congenitally blind children offer support for the latter position and suggest that a source of coherence in autism is restriction in certain forms of perceptually dependent social experience.

3D facial morphometry in children with oral clefts.

OBJECTIVES: The aim of this study was to characterize three-dimensional (3D) facial morphological variation of children with cleft lip and palate compared to an age- and sex-matched control group. DESIGN: Cross-sectional, case-controlled observational morphometric study. MATERIALS AND METHODS: Subjects were 103 children aged 8 to 12 years old with cleft lip and palate-40 with unilateral cleft lip and palate, 23 with unilateral cleft lip and alveolus, 19 with bilateral cleft lip and palate, and 21 with isolated cleft palate (ICP)-and 80 sex- and age-matched control subjects. Subjects were scanned using 3D stereophotogrammetry. Thirty-nine landmarks were digitized for each scan, and the x, y, and z coordinates for each landmark were extracted. Linear and angular facial measurements were computed. Multivariate analysis of covariance was undertaken to detect significant differences in facial morphometry between the groups. RESULTS: Statistically significant differences (P < .05) were observed between all groups. The greatest morphometrical impact was seen in those groups where both lip and palate were affected and repaired; the group with ICP was the most similar to the control subjects. CONCLUSIONS: Significant differences were seen in 3D soft-tissue measurements, mainly in the nasolabial region, between the cleft groups where the lip is affected and the ICP and control groups.

3D asymmetry of operated children with oral clefts.

OBJECTIVES: To explore three-dimensional (3D) facial asymmetry differences in operated children with oral clefts and to compare the results with a control group. SETTING AND SAMPLE POPULATION: The sample comprised one hundred and three 8- to 12-year-old children: 40 with unilateral cleft lip and palate (UCLP); 23 with unilateral cleft lip and alveolus (UCLA); 19 with bilateral cleft lip and palate (BCLP); 21 with cleft palate (CP) and 80 sex- and age-matched controls living in the North East of England. MATERIALS AND METHODS: 3D stereophotogrammetric facial scans were recorded for each participant at rest. Thirty-nine landmarks were recorded for each scan. The x, y and z coordinates for each landmark were extracted. Kruskal-Wallis and Mann-Whitney tests were conducted to identify 3D landmark asymmetry differences between the groups. RESULTS: Statistically significant differences were observed between all the groups. The UCLP and UCLA patients displayed the greatest asymmetry, followed by the BCLP group. The CP group was the least asymmetric among the cleft groups. Asymmetry was present to a lesser extent in the control group. CONCLUSIONS: Shape analysis indicates the possible differences in the aetiology and growth pattern of the CP group compared to UCLA or UCLP and BCLP groups.

Assessment of the significance of respiratory culture of Aspergillus in the non-neutropenic patient. A critique of published diagnostic criteria.

Assessment of the significance of isolation of Aspergillus sp. from respiratory culture in patients who are not neutropenic is a continuing problem in respiratory medicine. In recent years a number of criteria for defining patients with invasive or chronic pulmonary aspergillosis in this group have been proposed. This study sought to assess the value of three sets of these criteria in distinguishing between colonisation and aspergillosis requiring therapy when applied retrospectively to 121 patients with positive sputum or BAL culture for Aspergillus sp. Two patients (1.6%) were identified as having proven or probable aspergillosis by the EORTC criteria, two different patients fulfilled the criteria for invasive aspergillosis in the 62 patients with chronic obstructive pulmonary disease (3.2%), and yet another two different patients met the criteria for chronic pulmonary aspergillosis (1.6%). It is suggested that difficulties in the application of some of these criteria may prevent the accurate diagnosis of aspergillosis in the non-neutropenic patient setting.

The relation between social engagement and pretend play in autism.

The focus of this study is the nature and concomitants of pretend play among young children with autism. Age- and language-matched children with autism (n= 27), autism spectrum disorder (n= 14), and developmental disorders without autism (n= 16) were administered the Test of Pretend Play (ToPP; Lewis & Boucher, 1997), with an additional rating of 'playful pretence'. As predicted, children with autism showed less playful pretend than participants with developmental disorders who did not have autism. Across the groups, playful pretence was correlated with individual differences in communication and social interaction, even when scores on the ToPP were taken into account. Limitations in creative, playful pretend among children with autism relate to their restricted interpersonal communication and engagement.

Autism severity and qualities of parent-child relations.

The aim of this study was to examine how severity of autism affects children's interactions (relatedness) and relationships with their parents. Participants were 25 parent-child dyads that included offspring who were children with autism aged from 4 to 14 years. The severity of the children's autism was assessed using the calibrated severity metric of the Autism Diagnostic Observation Schedule (Gotham et al. in J Autism Dev Disord 39:693-705, 2009). Parent-child dyads were videotaped in 10-min semi-structured play interactions, and qualities of interpersonal relatedness were rated with the Dyadic Coding Scales (Humber and Moss in Am J Orthopsychiatr 75(1):128-141, 2005). Quality of relationships between parents and children were evaluated with a parent self-report measure, the Parent Child Relationship Inventory (Gerard in Parent-Child Relationship Inventory (PCRI) manual. WPS, Los Angeles, 1994). Multivariate regression analysis revealed that severity of autism was inversely related to patterns of parent-child interaction but not to reported quality of parent-child relationship. We consider the implications for thinking about relatedness and relationships among children with autism, and opportunities for intervention.

Dialogic linkage and resonance in autism.

We evaluated how children with autism make linguistic adjustments when talking with someone else. We devised two novel measures to assess (a) overall conversational linkage and (b) utterance-by-utterance resonance within dialogue between an adult and matched participants with and without autism (n = 12 per group). Participants with autism were less able to establish 'cognitive linkage' with an interlocutor. As predicted, only among children with autism was there a positive correlation between the ability to link in with speaker's meanings and ratings of emotional connectedness with the conversational partner. Participants with autism were not less likely to show a basic form of dialogic resonance across successive utterances (the 'frame grab'), but more often elaborated their responses in an atypical manner.

Treatment and outcome of Wilms' tumour patients: an analysis of all cases registered in the UKW3 trial.

BACKGROUND: The randomised findings of the UKW3 trial were that preoperative chemotherapy was associated with a more advantageous stage distribution and reduction in therapy burden versus immediate nephrectomy without compromising outcome in localised Wilms' tumour (WT). We analysed outcome in all WT registered in UKW3. PATIENTS AND METHODS: Seven hundred and eighteen WT cases (7% anaplastic) were registered in UKW3. We assigned a treatment stage and conducted survival analysis. RESULTS: Five-year event-free survival (EFS) and overall survival (OS) were 77.2% [95% confidence interval (CI) 73.9-80.2] and 87.5% (95% CI 84.8-89.7) after median follow-up of 9.5 years and 10.0 years, respectively. Five-year OS in localised non-anaplastic cases was 92.9% (95% CI 90.2-94.9). Anaplasia was associated with adverse outcome compared with non-anaplastic cases: 5-year EFS of 42.0% (95% CI 28.3-55.1) versus 79.8% (95% CI 76.5-82.7) and 5-year OS of 60% (95% CI 45.1-72.0) versus 89.6% (95% CI 87.0-91.7), respectively. Outcomes were similar for non-anaplastic stage I or II but significantly poorer in stage III cases than stage I. Five-year OS after relapse was 54.1% (95% CI 44.5-62.8). Forty-seven percent of non-anaplastic WT received anthracycline; 27% were treated with radiotherapy first line. CONCLUSION: These outcomes provide a baseline for future comparisons of WT treatment approach, burden and patient outcome.