Deducing the symmetry of helical assemblies: Applications to membrane proteins.

Helical reconstruction represents a convenient and powerful approach for structure determination of macromolecules that assemble into helical arrays. In the case of membrane proteins, formation of tubular crystals with helical symmetry represents an attractive alternative, especially when their small size precludes the use of single-particle analysis. An essential first step for helical reconstruction is to characterize the helical symmetry. This process is often daunting, due to the complexity of helical diffraction and to the low signal-to-noise ratio in images of individual assemblies. Furthermore, the large diameters of the tubular crystals produced by membrane proteins exacerbates the innate ambiguities that, if not resolved, will produce incorrect structures. In this report, we describe a set of tools that can be used to eliminate ambiguities and to validate the choice of symmetry. The first approach increases the signal-to-noise ratio along layer lines by incoherently summing data from multiple helical assemblies, thus producing several candidate indexing schemes. The second approach compares the layer lines from images with those from synthetic models built with the various candidate schemes. The third approach uses unit cell dimensions measured from collapsed tubes to distinguish between these candidate schemes. These approaches are illustrated with tubular crystals from a boron transporter from yeast, Bor1p, and a ß-barrel channel from the outer membrane of E. coli, OmpF.

Impact of the Enhanced Universal Support Offer to Care Homes during COVID-19 in the UK: Evaluation using appreciative inquiry.

There are over 2,300 care homes in the North East and Yorkshire Region, with rising rates of COVID-19 infection in April 2020. The Enhanced Universal Support Offer (EUSO) planned to improve support to care homes, working collaboratively with local integrated community services. Implementation was organised at 'place', through clinical commissioning and it was focused on leadership, prevention, additional clinical support, and workforce planning. The aim of the evaluation research was to understand the impact of the EUSO. The evaluation was co-produced by a group of senior leaders with additional academic involvement. An appreciative inquiry approach informed the interviews and focus groups with representative stakeholders. A thematic analysis using NVivo enabled a validation process and the data were charted into a systems framework. Data analysis resulted in five high level themes: Communication, Working Relationships, Systemic Perceptions, COVID-19 Implementation, and Organisational Support. Best practices were associated with joint working between health, local authority and care homes including medication optimisation and technology use. Care homes valued access to a named General Practitioner and community nursing working as a part of a wider multidisciplinary team. Conversely an overly reactive response to care homes combined with 'command and control' limited the benefits that were achieved. The EUSO was delivered at pace and resulted in an increased appreciation of the policy and principles of care home residents and workforce. The evaluation reflected a need to appreciate the care homes' knowledge and experience of resident wellbeing, and more fully involve them in the design of the support.

Use of ultrasound measurements to direct laparoscopic pyloromyotomy in infants.

BACKGROUND: Laparoscopic pyloromyotomy is associated with an increased risk of incomplete myotomy compared with open myotomy. We hypothesized that utilizing ultrasound measured length to direct laparoscopic pyloromyotomy would reduce the risk of incomplete pyloromyotomy without a concomitant increase in the risk of mucosal perforation. METHODS: Infants (n=43) with hypertrophic pyloric stenosis diagnosed by ultrasound and subsequent laparoscopic pyloromyotomy over a 2-year period (December 2006 through December 2008) were studied. Pyloromyotomy length was guided by preoperative ultrasound measurements. Pyloromyotomy was considered complete if the measured length was ≥ the ultrasound measurement. Infants were followed prospectively for time to full feeding, time to discharge, and complications. RESULTS: The cohort included 38 male and 5 female infants (age, 37±13 days; range, 17 to 72 days) who underwent ultrasound (length 1.9±0.2cm; thickness 4.4±0.9mm) and laparoscopic pyloromyotomy. Infants achieved full feeding 28±16 hours postoperatively and were discharged 34±18 hours postoperatively. No infant required reoperation for incomplete myotomy. One infant sustained mucosal perforation (2%). No patient suffered other complications. CONCLUSION: Preoperative ultrasound measurement of pyloric length to determine the length of laparoscopic pyloromyotomy, rather than visual cues alone, appears to minimize the risk of incomplete pyloromyotomy.

Preparing the child welfare workforce: Organizational commitment, identity, and desire to stay.

BACKGROUND: Since 1995, Colorado has had a Title IV-E child welfare Stipend Program, most recently involving four universities in partnership with the Colorado Department of Human Services. OBJECTIVE: A ten-year cohort study was conducted to understand program graduates' experiences with organizational commitment, the impact of stipends on child welfare professional identity and desire to remain in the child welfare field. PARTICIPANTS AND METHODS: The mixed methods evaluation involved 245 stipend graduates from 2006 to 2016 from Bachelor of Social Work (BSW) and Master of Social Work (MSW) programs and included an online survey and focus groups. RESULTS: Results indicate stipend graduates remained in the workforce beyond payback periods, felt prepared for the job, appreciated the skills and networks gained from their programs, and expressed gratitude for the financial assistance. Graduates identified workforce factors including peer support, supervisor support, and mobility in the agency as key retention sources for remaining in child welfare.

Crossing the clinical chasm: from the backpack to the palm.

Wake Area Health Education Center's RN Refresher program is designed to return RNs to practice. The purpose of this project was to focus on the use of the personal digital assistant (PDA) as a strategy to expedite the student's orientation to the clinical area. Nursing and library staff collaborated to research and purchase PDAs, along with clinical reference software, and provided these tools to RN Refresher students prior to the clinical practicum. Overall, students believed that the instruction was effective and were more comfortable with handheld computers. They also identified the most helpful software.

Assessing and treating vocal stereotypy in children with autism.

Previous research implies that stereotypic behavior tends to be maintained by the sensory consequences produced by engaging in the response. Few investigations, however, have focused on vocal stereotypy. The current study examined the noncommunicative vocalizations of 4 children with an autism spectrum disorder. First, functional analyses were conducted in an attempt to identify the function of each child's behavior. For each of the participants, it was found that vocal stereotypy was likely not maintained by the social consequences. Following assessment, response interruption and redirection (RIRD) was implemented in an ABAB design to determine whether vocal stereotypy could be successfully redirected. RIRD involved a teacher issuing a series of vocal demands the child readily complied with during regular academic programming. Vocal demands were presented contingent on the occurrence of vocal stereotypy and were continuously presented until the child complied with three consecutively issued demands without emitting vocal stereotypy. For each child, RIRD produced levels of vocal stereotypy substantially lower than those observed in baseline. For 3 of the children, an increase in appropriate communication was also observed. The children's teachers were trained to implement RIRD. Brief follow-up probes and anecdotal information implied that the treatment had a positive impact in the natural environment.

Structure of the SLC4 transporter Bor1p in an inward-facing conformation.

Bor1p is a secondary transporter in yeast that is responsible for boron transport. Bor1p belongs to the SLC4 family which controls bicarbonate exchange and pH regulation in animals as well as borate uptake in plants. The SLC4 family is more distantly related to members of the Amino acid-Polyamine-organoCation (APC) superfamily, which includes well studied transporters such as LeuT, Mhp1, AdiC, vSGLT, UraA, SLC26Dg. Their mechanism generally involves relative movements of two domains: a core domain that binds substrate and a gate domain that in many cases mediates dimerization. To shed light on conformational changes governing transport by the SLC4 family, we grew helical membrane crystals of Bor1p from Saccharomyces mikatae and determined a structure at ∼6 Šresolution using cryo-electron microscopy. To evaluate the conformation of Bor1p in these crystals, a homology model was built based on the related anion exchanger from red blood cells (AE1). This homology model was fitted to the cryo-EM density map using the Molecular Dynamics (MD) Flexible Fitting method and then relaxed by all-atom MD simulation in explicit solvent and membrane. Mapping of water accessibility indicates that the resulting structure represents an inward-facing conformation. Comparisons of the resulting Bor1p model with the X-ray structure of AE1 in an outward-facing conformation, together with MD simulations of inward-facing and outward-facing Bor1p models, suggest rigid body movements of the core domain relative to the gate domain. These movements are consistent with the rocking-bundle transport mechanism described for other members of the APC superfamily.

An Internet-based telerehabilitation system for the assessment of motor speech disorders: a pilot study.

PURPOSE: This pilot study explored the feasibility and effectiveness of an Internet-based telerehabilitation application for the assessment of motor speech disorders in adults with acquired neurological impairment. METHOD: Using a counterbalanced, repeated measures research design, 2 speech-language pathologists assessed 19 speakers with dysarthria on a battery of perceptual assessments. The assessments included a 19-item version of the Frenchay Dysarthria Assessment (FDA; P. Enderby, 1983), the Assessment of Intelligibility of Dysarthric Speech (K. M. Yorkston & D. R. Beukelman, 1981), perceptual analysis of a speech sample, and an overall rating of severity of the dysarthria. One assessment was conducted in the traditional face-to-face manner, whereas the other assessment was conducted using an online, custom-built telerehabilitation application. This application enabled real-time videoconferencing at 128 kb/s and the transfer of store-and-forward audio and video data between the speaker and speech-language pathologist sites. The assessment methods were compared using the J. M. Bland and D. G. Altman (1986, 1999) limits-of-agreement method and percentage level of agreement between the 2 methods. RESULTS: Measurements of severity of dysarthria, percentage intelligibility in sentences, and most perceptual ratings made in the telerehabilitation environment were found to fall within the clinically acceptable criteria. However, several ratings on the FDA were not comparable between the environments, and explanations for these results were explored. CONCLUSIONS: The online assessment of motor speech disorders using an Internet-based telerehabilitation system is feasible. This study suggests that with additional refinement of the technology and assessment protocols, reliable assessment of motor speech disorders over the Internet is possible. Future research methods are outlined.

On the role of preference in response competition.

A duration-based preference assessment identified items that matched and did not match the sensory consequences hypothesized to maintain stereotypy. When evaluated in treatment, these items effectively competed with the occurrence of stereotypy, regardless of their sensory properties. It is suggested that relative preference, as measured in duration-based assessment, can be as significant as type of stimulation produced in interventions that reduce automatically reinforced problem behavior.

Assessment of motor speech disorders online: a pilot study.

We have conducted a preliminary validation of an Internet-based telehealth application for assessing motor speech disorders in adults with acquired neurological impairment. The videoconferencing module used NetMeeting software to provide realtime videoconferencing through a 128 kbit/s Internet link, as well as the transfer of store-and-forward video and audio data from the participant to the clinician. Ten participants with dysarthria following acquired brain injury were included in the study. An assessment of the overall severity of the speech disturbance was made for each participant face to face (FTF) and in the online environment; in addition, a 23-item version of the Frenchay Dysarthria Assessment (FDA) (which measures motor speech function) and the Assessment of Intelligibility of Dysarthric Speech (ASSIDS) (which gives the percentage word and sentence intelligibility, words per minute and a rating of communication efficiency) were administered in both environments. There was a 90% level of agreement between the two assessment environments for the rating of overall severity of dysarthria. A 70-100% level of agreement was achieved for 17 (74%) of the 23 FDA variables. On the ASSIDS there was a significant difference between the FTF and online assessments only for percentage word intelligibility. These findings suggest that Internet-based assessment has potential as a reliable method for assessing motor speech disorders.

Persistence of stereotypic behavior: examining the effects of external reinforcers.

Basic research has shown that behavioral persistence is often positively related to rate of reinforcement. This relation, expressed in the metaphor of behavioral momentum, has potentially important implications for clinical application. The current study examined one prediction of the momentum metaphor for automatically reinforced behavior. Participants were 3 children who had been diagnosed with an autism spectrum disorder and who engaged in stereotypic behavior maintained by automatic reinforcement. Results suggested that stereotypic behavior was more resistant to disruption following periods of access to preferred stimuli delivered on a variable-time schedule than following periods without access to preferred stimuli. The implications of these findings for the treatment of automatically reinforced behavior are discussed.

Interdisciplinary rehabilitation outcomes following thrombolysis for acute ischaemic stroke: a case series.

BACKGROUND: Thrombolysis with recombinant tissue plasminogen activator (rtPA) is part of routine acute stroke clinical practice worldwide. Yet, it is unclear how rtPA influences specific rehabilitation outcomes, such as motor, cognitive and communication function. OBJECTIVE: The present study aimed to collect pilot data about the effects of rtPA on communication and motor recovery during the first three months post-rtPA. METHODS: Four individuals who received thrombolysis with rtPA for a single left hemisphere ischaemic stroke completed an assessment battery two weeks and three months post-stroke. Information pertaining to allied health service usage was also investigated. RESULTS: Reliable changes in assessment scores were observed for lower limb function in two participants with severe functional limitations. There was no reliable change in lower limb function for the two milder participants, or for any participants in upper limb or language function. Service usage varied between participants. Two participants required extensive inpatient rehabilitation. Three participants required outpatient or community rehabilitation. CONCLUSIONS: Tailoring of the service delivery approach may be required for individuals who receive rtPA based on functional limitations evident post-rtPA. Future research into the impact of rtPA on motor, cognitive and communication recovery after stroke is vital to inform rehabilitation programs and optimize outcomes.

Lowering developmental screening thresholds and raising quality improvement for preterm children.

OBJECTIVES: To determine: 1) if preterm children were referred, identified and received early intervention (EI)/ early childhood special education (ECSE) services at rates equivalent to term children after implementation of a universal, periodic Ages and Stages Questionnaire (ASQ) surveillance and screening system; 2) if pediatricians sufficiently lowered their screening thresholds with preterm children;and 3) if quality improvement opportunities exist. PATIENT AND METHODS: Secondary analysis was performed on 64 lower-risk, mostly late-preterm and 1363 term children who originally presented to their 12- or 24-month well- visits. Higher-risk preemies already involved with an EI agency/ identified with a delay were excluded. Board-certified pediatricians (N=18), and nurse practitioners (N = 2), blind to the ASQ results, were secondary participants. Differences between preterm and term developmental agency referrals were examined comparing Pediatric Developmental Impression to the ASQ under natural clinic conditions using a combined in-office or mail-back data collection protocol. Medical record and county EI/ECSE follow-up outcomes were conducted at 36 to 60 months. RESULTS: At 12 and 24 months, preterm (versus term) referral rates were 9.5%(versus 5.6%) with Pediatric Developmental Impression and 26.2% (versus 8.1%) with the ASQ. By 36 to 60 months, 37.5% of preterm (20.8% term) children were referred to EI/ECSE; of which, 50.0% of preterm (42.4% term) children were eligible for services, 54.2%of preterm children were identified with a developmental-behavioral disorder and 29.2% of preterm (20.8% term) children did not follow-up. For ASQ-only preterm referrals,55.6% were subsequently diagnosed with a developmental delay and/or disorder.Preterm children were 2 times more likely to be eligible than term children [corrected]. CONCLUSIONS: Combined referral, quality improvement and outcome data suggests that clinicians should lower their threshold for administering a psychometrically sound developmental screen when providing surveillance for ex-preemies. Quality improvement opportunities exist with diligent developmental surveillance and a more collaborative, standardized, reliable and interpersonal referral process.

The effects of response interruption and redirection and sertraline on vocal stereotypy.

Although response interruption and redirection (RIRD) has been shown to be successful in reducing vocal stereotypy, recent reports have suggested that selective serotonin reuptake inhibitors (SSRIs) may also reduce these behaviors. The purpose of the current investigation was to examine the effects of RIRD with and without sertraline on automatically maintained vocal stereotypy of a 4-year-old boy with autism. Results suggested that vocal stereotypy decreased when RIRD was implemented and that sertraline did not affect the participant's vocal stereotypy.

Complete colonic duplication--a case report.

Duplications of the entire colon are very rare. An 18-month-old boy presented with symptoms of chronic constipation and was noted with a complete colonic duplication. The presentation and management are discussed.