Evolutionary divergence times in the Annonaceae: evidence of a late Miocene origin of Pseuduvaria in Sundaland with subsequent diversification in New Guinea

<p>Abstract</p> <p>Background</p> <p>Phylogenetic analyses of the Annonaceae consistently identify four clades: a basal clade consisting of <it>Anaxagorea</it>, and a small 'ambavioid' clade that is sister to two main clades, the 'long branch clade' (LBC) and 'short branch clade' (SBC). Divergence times in the family have previously been estimated using non-parametric rate smoothing (NPRS) and penalized likelihood (PL). Here we use an uncorrelated lognormal (UCLD) relaxed molecular clock in BEAST to estimate diversification times of the main clades within the family with a focus on the Asian genus <it>Pseuduvaria </it>within the SBC. Two fossil calibration points are applied, including the first use of the recently discovered Annonaceae fossil <it>Futabanthus</it>. The taxonomy and morphology of <it>Pseuduvaria </it>have been well documented, although no previous dating or biogeographical studies have been undertaken. Ancestral areas at internal nodes within <it>Pseuduvaria </it>are determined using dispersal-vicariance analysis (DIVA) and weighted ancestral area analysis (WAAA).</p> <p>Results</p> <p>The divergence times of the main clades within the Annonaceae were found to deviate slightly from previous estimates that used different calibration points and dating methods. In particular, our estimate for the SBC crown (55.2-26.9 Mya) is much younger than previous estimates (62.5-53.1 ± 3.6 Mya and ca. 58.76 Mya). Early diversification of <it>Pseuduvaria </it>was estimated to have occurred 15-8 Mya, possibly associated with the 'mid-Miocene climatic optimum.' <it>Pseuduvaria </it>is inferred to have originated in Sundaland in the late Miocene, ca. 8 Mya; subsequent migration events were predominantly eastwards towards New Guinea and Australia, although several migratory reversals are also postulated. Speciation of <it>Pseuduvaria </it>within New Guinea may have occurred after ca. 6.5 Mya, possibly coinciding with the formation of the Central Range orogeny from ca. 8 Mya.</p> <p>Conclusion</p> <p>Our divergence time estimates within the Annonaceae are likely to be more precise as we used a UCLD clock model and calibrated the phylogeny using new fossil evidence. <it>Pseuduvaria </it>is shown to have dispersed from Sundaland after the late Miocene. The present-day paleotropical distribution of <it>Pseuduvaria </it>may have been achieved by long-distance dispersal, and speciation events might be explained by global climatic oscillations, sea level fluctuations, and tectonic activity.</p

Recommendations for a core outcome set for measuring standing balance in adult populations: a consensus-based approach

Standing balance is imperative for mobility and avoiding falls. Use of an excessive number of standing balance measures has limited the synthesis of balance intervention data and hampered consistent clinical practice.To develop recommendations for a core outcome set (COS) of standing balance measures for research and practice among adults.A combination of scoping reviews, literature appraisal, anonymous voting and face-to-face meetings with fourteen invited experts from a range of disciplines with international recognition in balance measurement and falls prevention. Consensus was sought over three rounds using pre-established criteria.The scoping review identified 56 existing standing balance measures validated in adult populations with evidence of use in the past five years, and these were considered for inclusion in the COS.Fifteen measures were excluded after the first round of scoring and a further 36 after round two. Five measures were considered in round three. Two measures reached consensus for recommendation, and the expert panel recommended that at a minimum, either the Berg Balance Scale or Mini Balance Evaluation Systems Test be used when measuring standing balance in adult populations.Inclusion of two measures in the COS may increase the feasibility of potential uptake, but poses challenges for data synthesis. Adoption of the standing balance COS does not constitute a comprehensive balance assessment for any population, and users should include additional validated measures as appropriate.The absence of a gold standard for measuring standing balance has contributed to the proliferation of outcome measures. These recommendations represent an important first step towards greater standardization in the assessment and measurement of this critical skill and will inform clinical research and practice internationally

SNPs Occur in Regions with Less Genomic Sequence Conservation

Rates of SNPs (single nucleotide polymorphisms) and cross-species genomic sequence conservation reflect intra- and inter-species variation, respectively. Here, I report SNP rates and genomic sequence conservation adjacent to mRNA processing regions and show that, as expected, more SNPs occur in less conserved regions and that functional regions have fewer SNPs. Results are confirmed using both mouse and human data. Regions include protein start codons, 3′ splice sites, 5′ splice sites, protein stop codons, predicted miRNA binding sites, and polyadenylation sites. Throughout, SNP rates are lower and conservation is higher at regulatory sites. Within coding regions, SNP rates are highest and conservation is lowest at codon position three and the fewest SNPs are found at codon position two, reflecting codon degeneracy for amino acid encoding. Exon splice sites show high conservation and very low SNP rates, reflecting both splicing signals and protein coding. Relaxed constraint on the codon third position is dramatically seen when separating exonic SNP rates based on intron phase. At polyadenylation sites, a peak of conservation and low SNP rate occurs from 30 to 17 nt preceding the site. This region is highly enriched for the sequence AAUAAA, reflecting the location of the conserved polyA signal. miRNA 3′ UTR target sites are predicted incorporating interspecies genomic sequence conservation; SNP rates are low in these sites, again showing fewer SNPs in conserved regions. Together, these results confirm that SNPs, reflecting recent genetic variation, occur more frequently in regions with less evolutionarily conservation

Malaria and other vector-borne infection surveillance in the U.S. Department of Defense Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance program: review of 2009 accomplishments

Vector-borne infections (VBI) are defined as infectious diseases transmitted by the bite or mechanical transfer of arthropod vectors. They constitute a significant proportion of the global infectious disease burden. United States (U.S.) Department of Defense (DoD) personnel are especially vulnerable to VBIs due to occupational contact with arthropod vectors, immunological naiveté to previously unencountered pathogens, and limited diagnostic and treatment options available in the austere and unstable environments sometimes associated with military operations. In addition to the risk uniquely encountered by military populations, other factors have driven the worldwide emergence of VBIs. Unprecedented levels of global travel, tourism and trade, and blurred lines of demarcation between zoonotic VBI reservoirs and human populations increase vector exposure. Urban growth in previously undeveloped regions and perturbations in global weather patterns also contribute to the rise of VBIs. The Armed Forces Health Surveillance Center-Global Emerging Infections Surveillance and Response System (AFHSC-GEIS) and its partners at DoD overseas laboratories form a network to better characterize the nature, emergence and growth of VBIs globally. In 2009 the network tested 19,730 specimens from 25 sites for Plasmodium species and malaria drug resistance phenotypes and nearly another 10,000 samples to determine the etiologies of non-Plasmodium species VBIs from regions spanning from Oceania to Africa, South America, and northeast, south and Southeast Asia. This review describes recent VBI-related epidemiological studies conducted by AFHSC-GEIS partner laboratories within the OCONUS DoD laboratory network emphasizing their impact on human populations

The impact of routine surveillance screening with magnetic resonance imaging (MRI) to detect tumour recurrence in children with central nervous system (CNS) tumours : Protocol for a systematic review and meta-analysis

Background: The aim of this study is to assess the impact of routine MRI surveillance to detect tumour recurrence in children with no new neurological signs or symptoms compared with alternative follow-up practices, including periodic clinical and physical examinations and the use of non-routine imaging upon presentation with disease signs or symptoms. Methods: Standard systematic review methods aimed at minimising bias will be employed for study identification, selection and data extraction. Ten electronic databases have been searched, and further citation searching and reference checking will be employed. Randomised and non-randomised controlled trials assessing the impact of routine surveillance MRI to detect tumour recurrence in children with no new neurological signs or symptoms compared to alternative follow-up schedules including imaging upon presentation with disease signs or symptoms will be included. The primary outcome is time to change in therapeutic intervention. Secondary outcomes include overall survival, surrogate survival outcomes, response rates, diagnostic yield per set of images, adverse events, quality of survival and validated measures of family psychological functioning and anxiety. Two reviewers will independently screen and select studies for inclusion. Quality assessment will be undertaken using the Cochrane Collaboration's tools for assessing risk of bias. Where possible, data will be summarised using combined estimates of effect for time to treatment change, survival outcomes and response rates using assumption-free methods. Further sub-group analyses and meta-regression models will be specified and undertaken to explore potential sources of heterogeneity between studies within each tumour type if necessary. Discussion: Assessment of the impact of surveillance imaging in children with CNS tumours is methodologically complex. The evidence base is likely to be heterogeneous in terms of imaging protocols, definitions of radiological response and diagnostic accuracy of tumour recurrence due to changes in imaging technology over time. Furthermore, the delineation of tumour recurrence from either pseudo-progression or radiation necrosis after radiotherapy is potentially problematic and linked to the timing of follow-up assessments. However, given the current routine practice of MRI surveillance in the follow-up of children with CNS tumours in the UK and the resource implications, it is important to evaluate the cost-benefit profile of this practice. Systematic review registration: PROSPERO CRD4201603680

A ‘telephone first’ approach to demand management in English general practice: a multimethod evaluation

Background: The increasing difficulty experienced by general practices in meeting patient demand is leading to new approaches being tried, including greater use of telephone consulting. Objectives: To evaluate a ‘telephone first’ approach, in which all patients requesting a general practitioner (GP) appointment are asked to speak to a GP on the telephone first. Methods: The study used a controlled before-and-after (time-series) approach using national reference data sets; it also incorporated economic and qualitative elements. There was a comparison between 146 practices using the ‘telephone first’ approach and control practices in England with regard to GP Patient Survey scores and secondary care utilisation (Hospital Episode Statistics). A practice manager survey was used in the ‘telephone first’ practices. There was an analysis of practice data and the patient surveys conducted in 20 practices using the ‘telephone first’ approach. Interviews were conducted with 43 patients and 49 primary care staff. The study also included an analysis of costs. Results: Following the introduction of the ‘telephone first’ approach, the average number of face-to-face consultations in practices decreased by 38% [95% confidence interval (CI) 29% to 45%; p < 0.0001], whereas there was a 12-fold increase in telephone consultations (95% CI 6.3-fold to 22.9-fold; p < 0.0001). The average durations of consultations decreased, which, when combined with the increased number of consultations, we estimate led to an overall increase of 8% in the mean time spent consulting by GPs, although there was a large amount of uncertainty (95% CI –1% to 17%; p = 0.0883). These average workload figures mask wide variation between practices, with some practices experiencing a substantial reduction in workload. Comparing ‘telephone first’ practices with control practices in England in terms of scores in the national GP Patient Survey, there was an improvement of 20 percentage points in responses to the survey question on length of time to get to see or speak to a doctor or nurse. Other responses were slightly negative. The introduction of the ‘telephone first’ approach was followed by a small (2%) increase in hospital admissions; there was no initial change in accident and emergency (A&E) department attendance, but there was a subsequent small (2%) decrease in the rate of increase in A&E attendances. We found no evidence that the ‘telephone first’ approach would produce net reductions in secondary care costs. Patients and staff expressed a wide range of both positive and negative views in interviews. Conclusions: The ‘telephone first’ approach shows that many problems in general practice can be dealt with on the telephone. However, the approach does not suit all patients and is not a panacea for meeting demand for care, and it is unlikely to reduce secondary care costs. Future research could include identifying how telephone consulting best meets the needs of different patient groups and practices in varying circumstances and how resources can be tailored to predictable patterns of demand.The National Institute for Health Research Health Services and Delivery Research programme

Identification of Spt5 Target Genes in Zebrafish Development Reveals Its Dual Activity In Vivo

Spt5 is a conserved essential protein that represses or stimulates transcription elongation in vitro. Immunolocalization studies on Drosophila polytene chromosomes suggest that Spt5 is associated with many loci throughout the genome. However, little is known about the prevalence and identity of Spt5 target genes in vivo during development. Here, we identify direct target genes of Spt5 using fogsk8 zebrafish mutant, which disrupts the foggy/spt5 gene. We identified that fogsk8 and their wildtype siblings differentially express less than 5% of genes examined. These genes participate in diverse biological processes from stress response to cell fate specification. Up-regulated genes exhibit shorter overall gene length compared to all genes examined. Through chromatin immunoprecipitation in zebrafish embryos, we identified a subset of developmentally critical genes that are bound by both Spt5 and RNA polymerase II. The protein occupancy patterns on these genes are characteristic of both repressive and stimulatory elongation regulation. Together our findings establish Spt5 as a dual regulator of transcription elongation in vivo and identify a small but diverse set of target genes critically dependent on Spt5 during development