Research Infrastructure Contact Zones: a framework and dataset to characterise the activities of major biodiversity informatics initiatives.

Background: The landscape of biodiversity data infrastructures and organisations is complex and fragmented. Many occupy specialised niches representing narrow segments of the multidimensional biodiversity informatics space, while others operate across a broad front, but differ from others by data type(s) handled, their geographic scope and the life cycle phase(s) of the data they support. In an effort to characterise the various dimensions of the biodiversity informatics landscape, we developed a framework and dataset to survey these dimensions for ten organisations (DiSSCo, GBIF, iBOL, Catalogue of Life, iNaturalist, Biodiversity Heritage Library, GeoCASe, LifeWatch, eLTER ELIXIR), relative to both their current activities and long-term strategic ambitions. New information: The survey assessed the contact between the infrastructure organisations by capturing the breadth of activities for each infrastructure across five categories (data, standards, software, hardware and policy), for nine types of data (specimens, collection descriptions, opportunistic observations, systematic observations, taxonomies, traits, geological data, molecular data and literature) and for seven phases of activity (creation, aggregation, access, annotation, interlinkage, analysis and synthesis). This generated a dataset of 6,300 verified observations, which have been scored and validated by leading members of each infrastructure organisation. The resulting data allow high-level questions about the overall biodiversity informatics landscape to be addressed, including the greatest gaps and contact between organisations.

A Pilot Study of a Parent-Mediated, Web-Based Motor Skill Intervention for Children With Down Syndrome: Project SKIP.

To inform the development of scalable and sustainable fundamental motor skill interventions for children with Down syndrome, this study examined the feasibility and preliminary effectiveness of Project Skill Intervention Implemented by Parents (Project SKIP), a web-based, parent-mediated intervention intended to improve ball skills among children with Down syndrome. Twenty-four families enrolled in the study (including 13 boys and 11 girls; Mage = 4.92). Fourteen children were assigned to an experimental group and participated in the 6-week intervention, and 10 children served as the inactive comparison group. The Test of Gross Motor Development-3 was administered preintervention and postintervention. In addition, parents of children in the experimental group completed a postintervention survey to assess their perceptions of Project SKIP. Following the intervention, there was a significant improvement in ball skills (p = .023, d = 0.86) for children in the experimental group, whereas the comparison group did not show significant improvement. Moreover, parents perceived Project SKIP to be feasible and effective; all parents reported being satisfied with their overall experience in the program, and 11 parents indicated that their child's fundamental motor skills were positively influenced by the intervention. Engagement was high, with the majority of parents (n = 8, 57%) interacting with Project SKIP content three to four times a week.

Double Up Food Bucks: A Qualitative Evaluation of Usage, Impact, Barriers, and Facilitators.

OBJECTIVE: Evaluate implementation of a farmers market-based fruit and vegetable incentive program. DESIGN: Four focus groups and 6 interviews with program participants from April through November 2017. SETTING: Double Up Food Bucks (DUFB) program in Western New York. PARTICIPANTS: Western New York DUFB program participants. PHENOMENON OF INTEREST: Customer DUFB usage, how DUFB affects purchasing, and program barriers or facilitators. ANALYSIS: Two independent researchers coded focus group and interview transcripts. Researchers summarized codes as themes and selected illustrative quotes. RESULTS: Participants (n = 36) were mostly female (75%); 69.4% reported a household income less than $20,000. They reported taking home and consuming more fruits and vegetables because of DUFB, almost always earning the maximum amount of DUFB and saving DUFB for later use. Barriers to using DUFB included limited hours and locations, running out of tokens, poor access to farmers market, and limited stocking. Participants recommended improved program communication, more venues, and convenient schedules to facilitate program use. CONCLUSIONS AND IMPLICATIONS: Findings indicated that incentive programs increased fruit and vegetable consumption and purchasing among those who use them, however barriers to using incentives still existed. To improve the participant experience, program administrators should implement technology-based systems, provide robust communication, and offer incentives at varied locations and times.

Efficacy of Cognitive Behavioral Therapy With and Without Medication for Adults With ADHD: A Randomized Clinical Trial.

Objective: Recent trials have demonstrated efficacy of cognitive behavioral therapy (CBT) in medicated adults with ADHD. Efficacy of CBT in unmedicated versus medicated adults remains mostly unknown. We evaluated the effects of group CBT alone versus combined with medication on ADHD symptoms and functional outcomes in adult patients. Method: Eighty-eight adults with ADHD received 12 manualized group CBT sessions, accompanied by individual coaching, either without (n = 46) or with (n = 42) medication. Treatment effects were evaluated following treatment and 3-month and 6-month follow-up using un-blinded self-report and observer ratings. Results: CBT + medication resulted in greater improvements than CBT alone in ADHD symptoms, organizational skills, and self-esteem. Group differences diminished over follow-up, as the CBT alone group continued improving, while the combined group maintained the gains. Conclusion: CBT + medication outperformed CBT alone for ADHD symptoms, organizational skills, and self-esteem, although its superiority tended to decrease over follow-up.

Effects of Simulated Horseback Riding on Balance, Postural Sway, and Quality of Life in Older Adults With Parkinson's Disease.

The purpose of this study was to determine changes in balance, postural sway, and quality of life after 6 wk of simulated horseback riding in adults diagnosed with Parkinson's disease. Eight older adults completed two 60-min riding sessions weekly for 6 wk. Variables of balance, postural sway, and quality of life were measured 6 wks before and within 1 wk before and after the intervention. Berg Balance Scale scores decreased from baseline to preintervention (48.36 ± 5.97 vs. 45.86 ± 6.42, p = .050) and increased from preintervention to postintervention (45.86 ± 6.42 vs. 50.00 ± 4.38, p = .002). Cognitive impairment, a dimension of quality of life, improved from baseline to postintervention (37.5 ± 20.5 vs. 21.5 ± 14.4, p = .007). Six weeks of simulated horseback riding may improve balance and cognitive impairment in older adults with Parkinson's disease.

New mechanism to identify cost savings in English NHS prescribing: minimising 'price per unit', a cross-sectional study.

BACKGROUND: Minimising prescription costs while maintaining quality is a core element of delivering high-value healthcare. There are various strategies to achieve savings, but almost no research to date on determining the most effective approach. We describe a new method of identifying potential savings due to large national variations in drug cost, including variation in generic drug cost, and compare these with potential savings from an established method (generic prescribing). METHODS: We used English National Health Service (NHS) Digital prescribing data, from October 2015 to September 2016. Potential cost savings were calculated by determining the price per unit (eg, pill, millilitre) for each drug and dose within each general practice. This was compared against the same cost for the practice at the lowest cost decile to determine achievable savings. We compared these price-per-unit savings to the savings possible from generic switching and determined the chemicals with the highest savings nationally. A senior pharmacist manually assessed whether a random sample of savings were practically achievable. RESULTS: We identified a theoretical maximum of £410 million of savings over 12 months. £273 million of these savings were for individual prescribing changes worth over £50 per practice per month (mean annual saving £33 433 per practice); this compares favourably with generic switching, where only £35 million of achievable savings were identified. The biggest savings nationally were on glucose blood testing reagents (£12 million), fluticasone propionate (£9 million) and venlafaxine (£8 million). Approximately half of all savings were deemed practically achievable. DISCUSSION: We have developed a new method to identify and enable large potential cost savings within NHS community prescribing. Given the current pressures on the NHS, it is vital that these potential savings are realised. Our tool enabling doctors to achieve these savings is now launched in pilot form at OpenPrescribing.net. However, savings could potentially be achieved more simply through national policy change.

The Differential Effects of Attentional Focus in Children with Moderate and Profound Visual Impairments.

It has been consistently reported that an external focus of attention leads to better motor performance than an internal focus, but no research to date has explored this effect in a population with visual impairments (VI). External focus statements typically reference something in the environment (e.g., target) that may be difficult to conceptualize for people with VI since they cannot generate a visual representation of the object of focus. Internal focus statements could be more closely identifiable with proprioception that is not impaired in this population. Recent studies have reported that sighted adults with temporarily obstructed vision are able to receive an external focus benefit when performing discrete tasks (i.e., golf putt and vertical jump), however, it is unclear if those with VI would experience the same benefit. The purpose of this investigation was to compare how an internal focus and external focus impact the balance of children with VI. Eighteen children with VI were grouped into a moderate (n = 11) and a profound VI group (n = 7). Participants completed a familiarization trial, an internal focus trial (i.e., focusing on feet) and an external focus trial (i.e., focusing on markers) in a counterbalanced order. The moderate VI group had a lower root mean square error while using an external focus (p = 0.04), while the profound VI group did not differ between conditions (p > 0.05). These results suggest that while performing a task reliant on sensory feedback, an external focus benefit may be dependent on the severity of VI. Further research is needed to examine whether external focus statements can be presented in a way that may be more intuitive to those with profound VI. These findings may help to influence how professionals in health-related fields (e.g., physical therapist and physical educators) give instructions on motor performance to populations with VI.

Use of technology to facilitate physical activity in children with autism spectrum disorders: A pilot study.

Deficits in social behavior and communication skills are correlated with reduced gross motor skills in children with autism spectrum disorders (ASD). The ExerciseBuddy application (EB app) was designed to communicate these motor skills to those with ASD and integrates evidence-based practices such as visual support and video modeling supported by The National Professional Development Center on Autism Spectrum Disorders. The purpose of this study was to determine the effectiveness of the EB app in facilitating increased physiologic responses to physical activity via a continuous measurement of energy expenditure and heart rate versus practice-style teaching methods in children with ASD. Six children, ages 5 to 10years, diagnosed with ASD were recruited. Each participant performed a variety of locomotor or object control skills as defined by the Test of Gross Motor Development-2 once per week for 4weeks. Motor skills were communicated and demonstrated using either practice-style teaching methods or the instructional section of the EB app. Energy expenditure and heart rate were measured continuously during each 12-minute session. A Wilcoxon signed-rank test was performed to assess any differences between the use of the app and practice-style teaching methods. The use of the EB app elicited greater values for peak energy expenditure (p=0.043) and peak heart rate response (p=0.028) while performing locomotor skills but no differences were observed while performing object control skills. Similarities were observed with average physiologic responses between the use of the EB app and practice-style teaching methods. The use of the EB app may allow for a greater peak physiologic response during more dynamic movements and a similar average cardiovascular and metabolic response when compared to practice-style teaching methods in children with ASD.

The public health approach to reducing suicide: opportunities for curriculum development in psychiatry residency training programs.

The authors review the current status of suicide prevention curricula in psychiatry training programs, describe the public health approach to suicide prevention, discuss public health strategies for reducing suicides and the unique role played by psychiatrists with respect to suicide prevention, and offer public health-oriented suicide prevention curriculum guidelines for psychiatry residents.

Evolutionary analysis and expression profiling of zebra finch immune genes.

Genes of the immune system are generally considered to evolve rapidly due to host-parasite coevolution. They are therefore of great interest in evolutionary biology and molecular ecology. In this study, we manually annotated 144 avian immune genes from the zebra finch (Taeniopygia guttata) genome and conducted evolutionary analyses of these by comparing them with their orthologs in the chicken (Gallus gallus). Genes classified as immune receptors showed elevated d(N)/d(S) ratios compared with other classes of immune genes. Immune genes in general also appear to be evolving more rapidly than other genes, as inferred from a higher d(N)/d(S) ratio compared with the rest of the genome. Furthermore, ten genes (of 27) for which sequence data were available from at least three bird species showed evidence of positive selection acting on specific codons. From transcriptome data of eight different tissues, we found evidence for expression of 106 of the studied immune genes, with primary expression of most of these in bursa, blood, and spleen. These immune-related genes showed a more tissue-specific expression pattern than other genes in the zebra finch genome. Several of the avian immune genes investigated here provide strong candidates for in-depth studies of molecular adaptation in birds.

Comorbidity in adults with attention-deficit hyperactivity disorder.

OBJECTIVE: To examine the prevalence of comorbid Axis I (current and lifetime) and II disorders in adult men and women with attention-deficit hyperactivity disorder (ADHD). METHOD: Adult patients (n = 447; 266 men, 181 women) received comprehensive assessments for ADHD and Axis I and II disorders. Adults were aged between 17 and 74 years. Among the patients diagnosed with ADHD (n = 335), there were those with ADHD inattentive subtype (ADHD-I) (n = 199), hyperactive-impulsive subtype (ADHD-H) (n = 24), or combined ADHD subtype (ADHD-C) (n = 112). Chi-square and logistic regression analyses were performed to examine associations between adults with and without ADHD on Axis I and II disorders. RESULTS: Adults with ADHD, compared with those without ADHD, had higher rates of Axis I (46.9% and 27.31%) and Axis II (50.7% and 38.2%) disorders. Adults with ADHD-C were more likely to have mood disorder, anxiety, conduct disorder, and substance use disorder as well as obsessive-compulsive personality disorder, passive-aggressive personality disorder, depressive personality disorder, narcissistic personality disorder, and borderline personality disorder (BPD). Men with ADHD were more likely to have antisocial personality disorder and had higher rates of current drug abuse than women with ADHD. Women with ADHD had higher rates of past and current panic disorder, and past anorexia and bulimia. Women with ADHD were more likely to have BPD than men with ADHD. CONCLUSIONS: Adults with ADHD have very high rates of comorbid Axis I and II disorders, with differences found between men and women on certain comorbid disorders.

Sequencing and association analysis of the type 1 diabetes-linked region on chromosome 10p12-q11.

BACKGROUND: In an effort to locate susceptibility genes for type 1 diabetes (T1D) several genome-wide linkage scans have been undertaken. A chromosomal region designated IDDM10 retained genome-wide significance in a combined analysis of the main linkage scans. Here, we studied sequence polymorphisms in 23 Mb on chromosome 10p12-q11, including the putative IDDM10 region, to identify genes associated with T1D. RESULTS: Initially, we resequenced the functional candidate genes, CREM and SDF1, located in this region, genotyped 13 tag single nucleotide polymorphisms (SNPs) and found no association with T1D. We then undertook analysis of the whole 23 Mb region. We constructed and sequenced a contig tile path from two bacterial artificial clone libraries. By comparison with a clone library from an unrelated person used in the Human Genome Project, we identified 12,058 SNPs. We genotyped 303 SNPs and 25 polymorphic microsatellite markers in 765 multiplex T1D families and followed up 22 associated polymorphisms in up to 2,857 families. We found nominal evidence of association in six loci (P = 0.05 - 0.0026), located near the PAPD1 gene. Therefore, we resequenced 38.8 kb in this region, found 147 SNPs and genotyped 84 of them in the T1D families. We also tested 13 polymorphisms in the PAPD1 gene and in five other loci in 1,612 T1D patients and 1,828 controls from the UK. Overall, only the D10S193 microsatellite marker located 28 kb downstream of PAPD1 showed nominal evidence of association in both T1D families and in the case-control sample (P = 0.037 and 0.03, respectively). CONCLUSION: We conclude that polymorphisms in the CREM and SDF1 genes have no major effect on T1D. The weak T1D association that we detected in the association scan near the PAPD1 gene may be either false or due to a small genuine effect, and cannot explain linkage at the IDDM10 region.

Accurate and reliable high-throughput detection of copy number variation in the human genome.

This study describes a new tool for accurate and reliable high-throughput detection of copy number variation in the human genome. We have constructed a large-insert clone DNA microarray covering the entire human genome in tiling path resolution that we have used to identify copy number variation in human populations. Crucial to this study has been the development of a robust array platform and analytic process for the automated identification of copy number variants (CNVs). The array consists of 26,574 clones covering 93.7% of euchromatic regions. Clones were selected primarily from the published "Golden Path," and mapping was confirmed by fingerprinting and BAC-end sequencing. Array performance was extensively tested by a series of validation assays. These included determining the hybridization characteristics of each individual clone on the array by chromosome-specific add-in experiments. Estimation of data reproducibility and false-positive/negative rates was carried out using self-self hybridizations, replicate experiments, and independent validations of CNVs. Based on these studies, we developed a variance-based automatic copy number detection analysis process (CNVfinder) and have demonstrated its robustness by comparison with the SW-ARRAY method.

Folate-sensitive fragile site FRA10A is due to an expansion of a CGG repeat in a novel gene, FRA10AC1, encoding a nuclear protein.

Fragile sites appear visually as nonstaining gaps on chromosomes that are inducible by specific cell culture conditions. Expansion of CGG/CCG repeats has been shown to be the molecular basis of all five folate-sensitive fragile sites characterized molecularly so far, i.e., FRAXA, FRAXE, FRAXF, FRA11B, and FRA16A. In the present study we have refined the localization of the FRA10A folate-sensitive fragile site by fluorescence in situ hybridization. Sequence analysis of a BAC clone spanning FRA10A identified a single, imperfect, but polymorphic CGG repeat that is part of a CpG island in the 5'UTR of a novel gene named FRA10AC1. The number of CGG repeats varied in the population from 8 to 13. Expansions exceeding 200 repeat units were methylated in all FRA10A fragile site carriers tested. The FRA10AC1 gene consists of 19 exons and is transcribed in the centromeric direction from the FRA10A repeat. The major transcript of approximately 1450 nt is ubiquitously expressed and codes for a highly conserved protein, FRA10AC1, of unknown function. Several splice variants leading to alternative 3' ends were identified (particularly in testis). These give rise to FRA10AC1 proteins with altered COOH-termini. Immunofluorescence analysis of full-length, recombinant EGFP-tagged FRA10AC1 protein showed that it was present exclusively in the nucleoplasm. We show that the expression of FRA10A, in parallel to the other cloned folate-sensitive fragile sites, is caused by an expansion and subsequent methylation of an unstable CGG trinucleotide repeat. Taking advantage of three cSNPs within the FRA10AC1 gene we demonstrate that one allele of the gene is not transcribed in a FRA10A carrier. Our data also suggest that in the heterozygous state FRA10A is likely a benign folate-sensitive fragile site.

Refined mapping of the HMSNR critical gene region--construction of a high-density integrated genetic and physical map.

Hereditary motor and sensory neuropathy russe, a form of autosomal recessive Charcot-Marie-Tooth disease, is a rare disorder found in several Roma families from Europe. The gene has been mapped to a 1Mb region on 10q22. Detailed analysis led to the exclusion of 22 candidate genes and the assembly of a high-density genetic map comprising 141 polymorphic markers. Extensive genotyping in an extended sample of affected families resulted in a 10-fold reduction of the critical hereditary motor and sensory neuropathy russe gene region, which is now contained within a single completely sequenced BAC clone. The fact that no sequence variant has been detected in the known genes in the critical region indicates that the hereditary motor and sensory neuropathy russe mutation affects a novel gene that remains to be identified.

Genomic sequence and transcriptional profile of the boundary between pericentromeric satellites and genes on human chromosome arm 10p.

Contiguous finished sequence from highly duplicated pericentromeric regions of human chromosomes is needed if we are to understand the role of pericentromeric instability in disease, and in gene and karyotype evolution. Here, we have constructed a BAC contig spanning the transition from pericentromeric satellites to genes on the short arm of human chromosome 10, and used this to generate 1.4 Mb of finished genomic sequence. Combining RT-PCR, in silico gene prediction, and paralogy analysis, we can identify two domains within the sequence. The proximal 600 kb consists of satellite-rich pericentromerically duplicated DNA which is transcript poor, containing only three unspliced transcripts. In contrast, the distal 850 kb contains four known genes (ZNF248, ZNF25, ZNF33A, and ZNF37A) and up to 32 additional transcripts of unknown function. This distal region also contains seven out of the eight intrachromosomal duplications within the sequence, including the p arm copy of the approximately 250-kb duplication which gave rise to ZNF33A and ZNF33B. By sequencing orthologs of the duplicated ZNF33 genes we have established that ZNF33A has diverged significantly at residues critical for DNA binding but ZNF33B has not, indicating that ZNF33B has remained constrained by selection for ancestral gene function. These results provide further evidence of gene formation within intrachromosomal duplications, but indicate that recent interchromosomal duplications at this centromere have involved transcriptionally inert, satellite rich DNA, which is likely to be heterochromatic. This suggests that any novel gene structures formed by these interchromosomal events would require relocation to a more open chromatin environment to be expressed.

Improving heart failure care: CMS' initiative. Improving heart failure care in outpatient practices.

This column is the eighth in a series reporting on the efforts of the Centers for Medicare & Medicaid Services ([CMS], formerly known as the Health Care Financing Administration), to improve care for Medicare beneficiaries with heart failure. Previous columns have focused on the hospital-based National Heart Failure project. An outpatient practice-based project, the Heart Failure Practice Improvement Effort (HF PIE), was described in the fourth and sixth columns. This column reports experience from the HF PIE project at the practice level in three states.

Mutations in the LGI1/Epitempin gene on 10q24 cause autosomal dominant lateral temporal epilepsy.

Autosomal dominant lateral temporal epilepsy (EPT; OMIM 600512) is a form of epilepsy characterized by partial seizures, usually preceded by auditory signs. The gene for this disorder has been mapped by linkage studies to chromosomal region 10q24. Here we show that mutations in the LGI1 gene segregate with EPT in two families affected by this disorder. Both mutations introduce premature stop codons and thus prevent the production of the full-length protein from the affected allele. By immunohistochemical studies, we demonstrate that the LGI1 protein, which contains several leucine-rich repeats, is expressed ubiquitously in the neuronal cell compartment of the brain. Moreover, we provide evidence for genetic heterogeneity within this disorder, since several other families with a phenotype consistent with this type of epilepsy lack mutations in the LGI1 gene.