Showing papers by "La Trobe University published in 2013"

An official American thoracic society/European respiratory society statement: Key concepts and advances in pulmonary rehabilitation

Abstract: Background: Pulmonary rehabilitation is recognized as a core component of the management of individuals with chronic respiratory disease. Since the 2006 American Thoracic Society (ATS)/European Respiratory Society (ERS) Statement on Pulmonary Rehabilitation, there has been considerable growth in our knowledge of its efficacy and scope. Purpose: The purpose of this Statement is to update the 2006 document, including a new definition of pulmonary rehabilitation and highlighting key concepts and major advances in the field. Methods: A multidisciplinary committee of experts representing the ATS Pulmonary Rehabilitation Assembly and the ERS Scientific Group 01.02, “Rehabilitation and Chronic Care,” determined the overall scope of this update through group consensus. Focused literature reviews in key topic areas were conducted by committee members with relevant clinical and scientific expertise. The final content of this Statement was agreed on by all members. Results: An updated definition of pulmonary rehabilitation is proposed. New data are presented on the science and application of pulmonary rehabilitation, including its effectiveness in acutely ill individuals with chronic obstructive pulmonary disease, and in individuals with other chronic respiratory diseases. The important role of pulmonary rehabilitation in chronic disease management is highlighted. In addition, the role of health behavior change in optimizing and maintaining benefits is discussed. Conclusions: The considerable growth in the science and application of pulmonary rehabilitation since 2006 adds further support for its efficacy in a wide range of individuals with chronic respiratory disease Read More: http://www.atsjournals.org/doi/abs/10.1164/rccm.201309-1634ST

Complete mitochondrial genome sequence of a Middle Pleistocene cave bear reconstructed from ultrashort DNA fragments

Abstract: Although an inverse relationship is expected in ancient DNA samples between the number of surviving DNA fragments and their length, ancient DNA sequencing libraries are strikingly deficient in molecules shorter than 40 bp. We find that a loss of short molecules can occur during DNA extraction and present an improved silica-based extraction protocol that enables their efficient retrieval. In combination with single-stranded DNA library preparation, this method enabled us to reconstruct the mitochondrial genome sequence from a Middle Pleistocene cave bear (Ursus deningeri) bone excavated at Sima de los Huesos in the Sierra de Atapuerca, Spain. Phylogenetic reconstructions indicate that the U. deningeri sequence forms an early diverging sister lineage to all Western European Late Pleistocene cave bears. Our results prove that authentic ancient DNA can be preserved for hundreds of thousand years outside of permafrost. Moreover, the techniques presented enable the retrieval of phylogenetically informative sequences from samples in which virtually all DNA is diminished to fragments shorter than 50 bp.

Pitfalls of predicting complex traits from SNPs

Abstract: The success of genome-wide association studies (GWASs) has led to increasing interest in making predictions of complex trait phenotypes, including disease, from genotype data. Rigorous assessment of the value of predictors is crucial before implementation. Here we discuss some of the limitations and pitfalls of prediction analysis and show how naive implementations can lead to severe bias and misinterpretation of results.

Discharge planning from hospital to home

Abstract: Background Discharge planning is a routine feature of health systems in many countries. The aim of discharge planning is to reduce hospital length of stay and unplanned readmission to hospital, and improve the co-ordination of services following discharge from hospital. Objectives To determine the effectiveness of planning the discharge of patients moving from hospital. Search strategy We updated the review using the Cochrane EPOC Group Trials Register, MEDLINE, EMBASE and the Social Science Citation Index (last searched in March 2009). Selection criteria Randomised controlled trials (RCTs) that compared an individualised discharge plan with routine discharge care that was not tailored to the individual patient. Participants were hospital inpatients. Data collection and analysis Two authors independently undertook data analysis and quality assessment using a predesigned data extraction sheet. Studies are grouped according to patient group (elderly medical patients, surgical patients and those with a mix of conditions) and by outcome. Main results Twenty-one RCTs (7234 patients) are included; ten of these were identified in this update. Fourteen trials recruited patients with a medical condition (4509 patients), four recruited patients with a mix of medical and surgical conditions (2225 patients), one recruited patients from a psychiatric hospital (343 patients), one from both a psychiatric hospital and from a general hospital (97 patients), and the final trial recruited patients admitted to hospital following a fall (60 patients). Hospital length of stay and readmissions to hospital were significantly reduced for patients allocated to discharge planning (mean difference length of stay -0.91, 95% CI -1.55 to -0.27, 10 trials; readmission rates RR 0.85, 95% CI 0.74 to 0.97, 11 trials). For elderly patients with a medical condition (usually heart failure) there was insufficient evidence for a difference in mortality (RR 1.04, 95% CI 0.74 to 1.46, four trials) or being discharged from hospital to home (RR 1.03, 95% CI 0.93 to 1.14, two trials). This was also the case for trials recruiting patients recovering from surgery and a mix of medical and surgical conditions. In three trials patients allocated to discharge planning reported increased satisfaction. There was little evidence on overall healthcare costs. Authors' conclusions The evidence suggests that a structured discharge plan tailored to the individual patient probably brings about small reductions in hospital length of stay and readmission rates for older people admitted to hospital with a medical condition. The impact of discharge planning on mortality, health outcomes and cost remains uncertain.

Comparative proteomics evaluation of plasma exosome isolation techniques and assessment of the stability of exosomes in normal human blood plasma

Abstract: Exosomes are nanovesicles released by a variety of cells and are detected in body fluids including blood. Recent studies have highlighted the critical application of exosomes as personalized targeted drug delivery vehicles and as reservoirs of disease biomarkers. While these research applications have created significant interest and can be translated into practice, the stability of exosomes needs to be assessed and exosome isolation protocols from blood plasma need to be optimized. To optimize methods to isolate exosomes from blood plasma, we performed a comparative evaluation of three exosome isolation techniques (differential centrifugation coupled with ultracentrifugation, epithelial cell adhesion molecule immunoaffinity pull-down, and OptiPrep(TM) density gradient separation) using normal human plasma. Based on MS, Western blotting and microscopy results, we found that the OptiPrep(TM) density gradient method was superior in isolating pure exosomal populations, devoid of highly abundant plasma proteins. In addition, we assessed the stability of exosomes in plasma over 90 days under various storage conditions. Western blotting analysis using the exosomal marker, TSG101, revealed that exosomes are stable for 90 days. Interestingly, in the context of cellular uptake, the isolated exosomes were able to fuse with target cells revealing that they were indeed biologically active.

StAMPP: an R package for calculation of genetic differentiation and structure of mixed-ploidy level populations.

Abstract: Statistical Analysis of Mixed-Ploidy Populations (StAMPP) is a freely available R package for calculation of population structure and differentiation based on single nucleotide polymorphism (SNP) genotype data from populations of any ploidy level, and/or mixed-ploidy levels. StAMPP provides an advance on previous similar software packages, due to an ability to calculate pairwise FST values along with confidence intervals, Nei's genetic distance and genomic relationship matrixes from data sets of mixed-ploidy level. The software code is designed to efficiently handle analysis of large genotypic data sets that are typically generated by high-throughput genotyping platforms. Population differentiation studies using StAMPP are broadly applicable to studies of molecular ecology and conservation genetics, as well as animal and plant breeding.

Psychological responses matter in returning to preinjury level of sport after anterior cruciate ligament reconstruction surgery.

Abstract: Background:Up to two-thirds of athletes may not return to their preinjury level of sport by 12 months after anterior cruciate ligament (ACL) reconstruction surgery, despite being physically recovered. This has led to questions about what other factors may influence return to sport.Purpose:To determine whether psychological factors predicted return to preinjury level of sport by 12 months after ACL reconstruction surgery.Study Design:Case control study; Level of evidence, 3.Methods:Recreational and competitive-level athletes seen at a private orthopaedic clinic with an ACL injury were consecutively recruited. The primary outcome was return to the preinjury level of sports participation. The psychological factors evaluated were psychological readiness to return to sport, fear of reinjury, mood, emotions, sport locus of control, and recovery expectations. Participants were followed up preoperatively and at 4 and 12 months postoperatively.Results:In total, 187 athletes participated. At 12 months, 56 athletes ...

The Case for Using the Repeatability Coefficient When Calculating Test–Retest Reliability

Abstract: The use of standardised tools is an essential component of evidence-based practice. Reliance on standardised tools places demands on clinicians to understand their properties, strengths, and weaknesses, in order to interpret results and make clinical decisions. This paper makes a case for clinicians to consider measurement error (ME) indices Coefficient of Repeatability (CR) or the Smallest Real Difference (SRD) over relative reliability coefficients like the Pearson’s (r) and the Intraclass Correlation Coefficient (ICC), while selecting tools to measure change and inferring change as true. The authors present statistical methods that are part of the current approach to evaluate test–retest reliability of assessment tools and outcome measurements. Selected examples from a previous test–retest study are used to elucidate the added advantages of knowledge of the ME of an assessment tool in clinical decision making. The CR is computed in the same units as the assessment tool and sets the boundary of the minimal detectable true change that can be measured by the tool.

How insulin engages its primary binding site on the insulin receptor

Abstract: Insulin receptor signalling has a central role in mammalian biology, regulating cellular metabolism, growth, division, differentiation and survival. Insulin resistance contributes to the pathogenesis of type 2 diabetes mellitus and the onset of Alzheimer's disease; aberrant signalling occurs in diverse cancers, exacerbated by cross-talk with the homologous type 1 insulin-like growth factor receptor (IGF1R). Despite more than three decades of investigation, the three-dimensional structure of the insulin-insulin receptor complex has proved elusive, confounded by the complexity of producing the receptor protein. Here we present the first view, to our knowledge, of the interaction of insulin with its primary binding site on the insulin receptor, on the basis of four crystal structures of insulin bound to truncated insulin receptor constructs. The direct interaction of insulin with the first leucine-rich-repeat domain (L1) of insulin receptor is seen to be sparse, the hormone instead engaging the insulin receptor carboxy-terminal α-chain (αCT) segment, which is itself remodelled on the face of L1 upon insulin binding. Contact between insulin and L1 is restricted to insulin B-chain residues. The αCT segment displaces the B-chain C-terminal β-strand away from the hormone core, revealing the mechanism of a long-proposed conformational switch in insulin upon receptor engagement. This mode of hormone-receptor recognition is novel within the broader family of receptor tyrosine kinases. We support these findings by photo-crosslinking data that place the suggested interactions into the context of the holoreceptor and by isothermal titration calorimetry data that dissect the hormone-insulin receptor interface. Together, our findings provide an explanation for a wealth of biochemical data from the insulin receptor and IGF1R systems relevant to the design of therapeutic insulin analogues.

Telerehabilitation services for stroke.

Abstract: Background Telerehabilitation is an alternative way of delivering rehabilitation services. Information and communication technologies are used to facilitate communication between the healthcare professional and the patient in a remote location. The use of telerehabilitation is becoming more viable as the speed and sophistication of communication technologies improve. However, it is currently unclear how effective this model of delivery is relative to rehabilitation delivered face-to-face. Objectives To determine whether the use of telerehabilitation leads to improved ability to perform activities of daily living amongst stroke survivors when compared with (1) in-person rehabilitation (when the clinician and the patient are at the same physical location and rehabilitation is provided face-to-face); or (2) no rehabilitation. Secondary objectives were to determine whether use of telerehabilitation leads to greater independence in self care and domestic life and improved mobility, health-related quality of life, upper limb function, cognitive function or functional communication when compared with in-person rehabilitation and no rehabilitation. Additionally, we aimed to report on the presence of adverse events, cost-effectiveness, feasibility and levels of user satisfaction associated with telerehabilitation interventions. Search methods We searched the Cochrane Stroke Group Trials Register (November 2012), the Cochrane Effective Practice and Organization of Care Group Trials Register (November 2012), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 11, 2012), MEDLINE (1950 to November 2012), EMBASE (1980 to November 2012) and eight additional databases. We searched trial registries, conference proceedings and reference lists. Selection criteria Randomised controlled trials (RCTs) of telerehabilitation in stroke. We included studies that compared telerehabilitation with in-person rehabilitation or no rehabilitation. In addition, we synthesised and described the results of RCTs that compared two different methods of delivering telerehabilitation services without an alternative group. We included rehabilitation programmes that used a combination of telerehabilitation and in-person rehabilitation provided that the greater proportion of intervention was provided via telerehabilitation. Data collection and analysis Two review authors independently identified trials on the basis of prespecified inclusion criteria, extracted data and assessed risk of bias. A third review author moderated any disagreements. The review authors contacted investigators to ask for missing information. Main results We included in the review 10 trials involving a total of 933 participants. The studies were generally small, and reporting quality was often inadequate, particularly in relation to blinding of outcome assessors and concealment of allocation. Selective outcome reporting was apparent in several studies. Study interventions and comparisons varied, meaning that in most cases, it was inappropriate to pool studies. Intervention approaches included upper limb training, lower limb and mobility retraining, case management and caregiver support. Most studies were conducted with people in the chronic phase following stroke. Primary outcome: no statistically significant results for independence in activities of daily living (based on two studies with 661 participants) were noted when a case management intervention was evaluated. Secondary outcomes: no statistically significant results for upper limb function (based on two studies with 46 participants) were observed when a computer programme was used to remotely retrain upper limb function. Evidence was insufficient to draw conclusions on the effects of the intervention on mobility, health-related quality of life or participant satisfaction with the intervention. No studies evaluated the cost-effectiveness of telerehabilitation. No studies reported on the occurrence of adverse events within the studies. Authors' conclusions We found insufficient evidence to reach conclusions about the effectiveness of telerehabilitation after stroke. Moreover, we were unable to find any randomised trials that included an evaluation of cost-effectiveness. Which intervention approaches are most appropriately adapted to a telerehabilitation approach remain unclear, as does the best way to utilise this approach.

Exercise rehabilitation for patients with critical illness: a randomized controlled trial with 12 months of follow-up

Abstract: The purpose of this trial was to investigate the effectiveness of an exercise rehabilitation program commencing during ICU admission and continuing into the outpatient setting compared with usual care on physical function and health-related quality of life in ICU survivors. We conducted a single-center, assessor-blinded, randomized controlled trial. One hundred and fifty participants were stratified and randomized to receive usual care or intervention if they were in the ICU for 5 days or more and had no permanent neurological insult. The intervention group received intensive exercises in the ICU and the ward and as outpatients. Participants were assessed at recruitment, ICU admission, hospital discharge and at 3-, 6- and 12-month follow-up. Physical function was evaluated using the Six-Minute Walk Test (6MWT) (primary outcome), the Timed Up and Go Test and the Physical Function in ICU Test. Patient-reported outcomes were measured using the Short Form 36 Health Survey, version 2 (SF-36v2) and Assessment of Quality of Life (AQoL) Instrument. Data were analyzed using mixed models. The a priori enrollment goal was not reached. There were no between-group differences in demographic and hospital data, including acuity and length of acute hospital stay (LOS) (Acute Physiology and Chronic Health Evaluation II score: 21 vs 19; hospital LOS: 20 vs 24 days). No significant differences were found for the primary outcome of 6MWT or any other outcomes at 12 months after ICU discharge. However, exploratory analyses showed the rate of change over time and mean between-group differences in 6MWT from first assessment were greater in the intervention group. Further research examining the trajectory of improvement with rehabilitation is warranted in this population. The trial was registered with the Australian New Zealand Clinical Trials Registry ACTRN12605000776606 .

Maternal feeding practices predict weight gain and obesogenic eating behaviors in young children: a prospective study.

Abstract: Maternal feeding practices have been proposed to play an important role in early child weight gain and obesogenic eating behaviors. However, to date longitudinal investigations in young children exploring these relationships have been lacking. The aim of the present study was to explore prospective relationships between maternal feeding practices, child weight gain and obesogenic eating behaviors in 2-year-old children. The competing hypothesis that child eating behaviors predict changes in maternal feeding practices was also examined. A sample of 323 mother (mean age = 35 years, ± 0.37) and child dyads (mean age = 2.03 years, ± 0.37 at recruitment) were participants. Mothers completed a questionnaire assessing parental feeding practices and child eating behaviors at baseline and again one year later. Child BMI (predominantly objectively measured) was obtained at both time points. Increases in child BMI z-scores over the follow-up period were predicted by maternal instrumental feeding practices. Furthermore, restriction, emotional feeding, encouragement to eat, weight-based restriction and fat restriction were associated prospectively with the development of obesogenic eating behaviors in children including emotional eating, tendency to overeat and food approach behaviors (such as enjoyment of food and good appetite). Maternal monitoring, however, predicted decreases in food approach eating behaviors. Partial support was also observed for child eating behaviors predicting maternal feeding practices. Maternal feeding practices play an important role in the development of weight gain and obesogenic eating behaviors in young children and are potential targets for effective prevention interventions aiming to decrease child obesity.

Association rule mining to detect factors which contribute to heart disease in males and females

Abstract: This paper investigates the sick and healthy factors which contribute to heart disease for males and females. Association rule mining, a computational intelligence approach, is used to identify these factors and the UCI Cleveland dataset, a biological database, is considered along with the three rule generation algorithms - Apriori, Predictive Apriori and Tertius. Analyzing the information available on sick and healthy individuals and taking confidence as an indicator, females are seen to have less chance of coronary heart disease then males. Also, the attributes indicating healthy and sick conditions were identified. It is seen that factors such as chest pain being asymptomatic and the presence of exercise-induced angina indicate the likely existence of heart disease for both men and women. However, resting ECG being either normal or hyper and slope being flat are potential high risk factors for women only. For men, on the other hand, only a single rule expressing resting ECG being hyper was shown to be a significant factor. This means, for women, resting ECG status is a key distinct factor for heart disease prediction. Comparing the healthy status of men and women, slope being up, number of coloured vessels being zero, and oldpeak being less than or equal to 0.56 indicate a healthy status for both genders.

A systematic review of the psychological factors associated with returning to sport following injury

Abstract: Background Psychological factors have been shown to be associated with the recovery and rehabilitation period following sports injury, but less is known about the psychological response associated with returning to sport after injury. The aim of this review was to identify psychological factors associated with returning to sport following sports injury evaluated with the self-determination theory framework. Study design Systematic review. Method Electronic databases were searched from the earliest possible entry to March 2012. Quantitative studies were reviewed that included athletes who had sustained an athletic injury, reported the return to sport rate and measured at least one psychological variable. The risk of bias in each study was appraised with a quality checklist. Results Eleven studies that evaluated 983 athletes and 15 psychological factors were included for review. The three central elements of self-determination theory—autonomy, competence and relatedness were found to be related to returning to sport following injury. Positive psychological responses including motivation, confidence and low fear were associated with a greater likelihood of returning to the preinjury level of participation and returning to sport more quickly. Fear was a prominent emotional response at the time of returning to sport despite the fact that overall emotions became more positive as recovery and rehabilitation progressed. Conclusions There is preliminary evidence that positive psychological responses are associated with a higher rate of returning to sport following athletic injury, and should be taken into account by clinicians during rehabilitation.

Risk factors for hamstring muscle strain injury in sport: a systematic review and meta-analysis

Abstract: Hamstring muscle strain-type injuries are common in sports that involve sprinting,1 acceleration, deceleration, rapid change in direction and jumping.2 ,3 Occurring in both recreational and professional sports, these injuries can result in substantial time lost from sport and commonly recur.4 ,5 In the Australian Football League (AFL), hamstring muscle strain-type injuries have displayed a high incidence rate, with a 10 year mean of 6.1 new injuries per club each year and a 23% average recurrence rate.6 A recurrence rate of 17% has been reported in elite soccer players7 with hamstring injuries also recorded as the most common injury accounting for 12% of all injuries and resulting in an average of four missed games per injury.8 The high incidence of hamstring muscle strain-type injuries and potential associated costs has resulted in a substantial amount of research into the factors related to such injuries. Two recent systematic reviews have been completed in an attempt to collate the evidence around risk factors for hamstring injuries.9 ,10 Both reviews identified hamstring muscle weakness and thigh muscle imbalance, muscle flexibility, previous hamstring injury, other previous injury and age as potential risk factors; however, these reviews concluded that single variables were inconsistently identified as associated factors. Both reviews provided a qualitative synthesis of the literature and included risk factor studies as well as intervention studies, where a potential risk factor was modified with a training programme. The inclusion of intervention studies may potentially complicate risk factor analyses, as such studies assume that the factor being modified is associated with the injury and that the factor can be modified by the treatment programme. The aim of the current review was to assemble all available knowledge and data to identify the intrinsic and extrinsic risk factors associated with …

Proteome profiling of exosomes derived from human primary and metastatic colorectal cancer cells reveal differential expression of key metastatic factors and signal transduction components

Abstract: Exosomes are small extracellular 40-100 nm diameter membrane vesicles of late endosomal origin that can mediate intercellular transfer of RNAs and proteins to assist premetastatic niche formation. Using primary (SW480) and metastatic (SW620) human isogenic colorectal cancer cell lines we compared exosome protein profiles to yield valuable insights into metastatic factors and signaling molecules fundamental to tumor progression. Exosomes purified using OptiPrep™ density gradient fractionation were 40-100 nm in diameter, were of a buoyant density ~1.09 g/mL, and displayed stereotypic exosomal markers TSG101, Alix, and CD63. A major finding was the selective enrichment of metastatic factors (MET, S100A8, S100A9, TNC), signal transduction molecules (EFNB2, JAG1, SRC, TNIK), and lipid raft and lipid raft-associated components (CAV1, FLOT1, FLOT2, PROM1) in exosomes derived from metastatic SW620 cells. Additionally, using cryo-electron microscopy, ultrastructural components in exosomes were identified. A key finding of this study was the detection and colocalization of protein complexes EPCAM-CLDN7 and TNIK-RAP2A in colorectal cancer cell exosomes. The selective enrichment of metastatic factors and signaling pathway components in metastatic colon cancer cell-derived exosomes contributes to our understanding of the cross-talk between tumor and stromal cells in the tumor microenvironment.

The increase in global HIV epidemics in MSM.

Abstract: Epidemics of HIV in MSM continue to expand in most low, middle, and upper income countries in 2013 and rates of new infection have been consistently high among young MSM. Current prevention and treatment strategies are insufficient for this next wave of HIV spread. We conducted a series of comprehensive reviews of HIV prevalence and incidence, risks for HIV, prevention and care, stigma and discrimination, and policy and advocacy options. The high per act transmission probability of receptive anal intercourse, sex role versatility among MSM, network level effects, and social and structural determinants play central roles in disproportionate disease burdens. HIV can be transmitted through large MSM networks at great speed. Molecular epidemiologic data show marked clustering of HIV in MSM networks, and high proportions of infections due to transmission from recent infections. Prevention strategies that lower biological risks, including those using antiretrovirals, offer promise for epidemic control, but are limited by structural factors including, discrimination, criminalization, and barriers to healthcare. Subepidemics, including among racial and ethnic minority MSM in the United States and UK, are particularly severe and will require culturally tailored efforts. For the promise of new and combined bio-behavioral interventions to be realized, clinically competent healthcare is necessary and community leadership, engagement, and empowerment are likely to be key. Addressing the expanding epidemics of HIV in MSM will require continued research, increased resources, political will, policy change, structural reform, community engagement, and strategic planning and programming, but it can and must be done.

The Membrane-Bound NAC Transcription Factor ANAC013 Functions in Mitochondrial Retrograde Regulation of the Oxidative Stress Response in Arabidopsis

Abstract: Upon disturbance of their function by stress, mitochondria can signal to the nucleus to steer the expression of responsive genes. This mitochondria-to-nucleus communication is often referred to as mitochondrial retrograde regulation (MRR). Although reactive oxygen species and calcium are likely candidate signaling molecules for MRR, the protein signaling components in plants remain largely unknown. Through meta-analysis of transcriptome data, we detected a set of genes that are common and robust targets of MRR and used them as a bait to identify its transcriptional regulators. In the upstream regions of these mitochondrial dysfunction stimulon (MDS) genes, we found a cis-regulatory element, the mitochondrial dysfunction motif (MDM), which is necessary and sufficient for gene expression under various mitochondrial perturbation conditions. Yeast one-hybrid analysis and electrophoretic mobility shift assays revealed that the transmembrane domain-containing no apical meristem/Arabidopsis transcription activation factor/cup-shaped cotyledon transcription factors (ANAC013, ANAC016, ANAC017, ANAC053, and ANAC078) bound to the MDM cis-regulatory element. We demonstrate that ANAC013 mediates MRR-induced expression of the MDS genes by direct interaction with the MDM cis-regulatory element and triggers increased oxidative stress tolerance. In conclusion, we characterized ANAC013 as a regulator of MRR upon stress in Arabidopsis thaliana.

Pulling out the 1%: Whole-Genome Capture for the Targeted Enrichment of Ancient DNA Sequencing Libraries

Abstract: Most ancient specimens contain very low levels of endogenous DNA, precluding the shotgun sequencing of many interesting samples because of cost. Ancient DNA (aDNA) libraries often contain <1% endogenous DNA, with the majority of sequencing capacity taken up by environmental DNA. Here we present a capture-based method for enriching the endogenous component of aDNA sequencing libraries. By using biotinylated RNA baits transcribed from genomic DNA libraries, we are able to capture DNA fragments from across the human genome. We demonstrate this method on libraries created from four Iron Age and Bronze Age human teeth from Bulgaria, as well as bone samples from seven Peruvian mummies and a Bronze Age hair sample from Denmark. Prior to capture, shotgun sequencing of these libraries yielded an average of 1.2% of reads mapping to the human genome (including duplicates). After capture, this fraction increased substantially, with up to 59% of reads mapped to human and enrichment ranging from 6- to 159-fold. Furthermore, we maintained coverage of the majority of regions sequenced in the precapture library. Intersection with the 1000 Genomes Project reference panel yielded an average of 50,723 SNPs (range 3,062–147,243) for the postcapture libraries sequenced with 1 million reads, compared with 13,280 SNPs (range 217–73,266) for the precapture libraries, increasing resolution in population genetic analyses. Our whole-genome capture approach makes it less costly to sequence aDNA from specimens containing very low levels of endogenous DNA, enabling the analysis of larger numbers of samples.

Riparian Ecosystems in the 21st Century: Hotspots for Climate Change Adaptation?

Abstract: Riparian ecosystems in the 21st century are likely to play a critical role in determining the vulnerability of natural and human systems to climate change, and in influencing the capacity of these systems to adapt. Some authors have suggested that riparian ecosystems are particularly vulnerable to climate change impacts due to their high levels of exposure and sensitivity to climatic stimuli, and their history of degradation. Others have highlighted the probable resilience of riparian ecosystems to climate change as a result of their evolution under high levels of climatic and environmental variability. We synthesize current knowledge of the vulnerability of riparian ecosystems to climate change by assessing the potential exposure, sensitivity, and adaptive capacity of their key components and processes, as well as ecosystem functions, goods and services, to projected global climatic changes. We review key pathways for ecological and human adaptation for the maintenance, restoration and enhancement of riparian ecosystem functions, goods and services and present emerging principles for planned adaptation. Our synthesis suggests that, in the absence of adaptation, riparian ecosystems are likely to be highly vulnerable to climate change impacts. However, given the critical role of riparian ecosystem functions in landscapes, as well as the strong links between riparian ecosystems and human well-being, considerable means, motives and opportunities for strategically planned adaptation to climate change also exist. The need for planned adaptation of and for riparian ecosystems is likely to be strengthened as the importance of many riparian ecosystem functions, goods and services will grow under a changing climate. Consequently, riparian ecosystems are likely to become adaptation ‘hotspots’ as the century unfolds.

A Membrane-Bound NAC Transcription Factor, ANAC017, Mediates Mitochondrial Retrograde Signaling in Arabidopsis

Abstract: Plants require daily coordinated regulation of energy metabolism for optimal growth and survival and therefore need to integrate cellular responses with both mitochondrial and plastid retrograde signaling. Using a forward genetic screen to characterize regulators of alternative oxidase1a (rao) mutants, we identified RAO2/Arabidopsis NAC domain-containing protein17 (ANAC017) as a direct positive regulator of AOX1a. RAO2/ANAC017 is targeted to connections and junctions in the endoplasmic reticulum (ER) and F-actin via a C-terminal transmembrane (TM) domain. A consensus rhomboid protease cleavage site is present in ANAC017 just prior to the predicted TM domain. Furthermore, addition of the rhomboid protease inhibitor N-p-Tosyl-l-Phe chloromethyl abolishes the induction of AOX1a upon antimycin A treatment. Simultaneous fluorescent tagging of ANAC017 with N-terminal red fluorescent protein (RFP) and C-terminal green fluorescent protein (GFP) revealed that the N-terminal RFP domain migrated into the nucleus, while the C-terminal GFP tag remained in the ER. Genome-wide analysis of the transcriptional network regulated by RAO2/ANAC017 under stress treatment revealed that RAO2/ANAC017 function was necessary for >85% of the changes observed as a primary response to cytosolic hydrogen peroxide (H2O2), but only ~33% of transcriptional changes observed in response to antimycin A treatment. Plants with mutated rao2/anac017 were more stress sensitive, whereas a gain-of-function mutation resulted in plants that had lower cellular levels of H2O2 under untreated conditions.

Ultrafast three-dimensional imaging of lattice dynamics in individual gold nanocrystals

Abstract: Key insights into the behavior of materials can be gained by observing their structure as they undergo lattice distortion. Laser pulses on the femtosecond time scale can be used to induce disorder in a "pump-probe" experiment with the ensuing transients being probed stroboscopically with femtosecond pulses of visible light, x-rays, or electrons. Here we report three-dimensional imaging of the generation and subsequent evolution of coherent acoustic phonons on the picosecond time scale within a single gold nanocrystal by means of an x-ray free-electron laser, providing insights into the physics of this phenomenon. Our results allow comparison and confirmation of predictive models based on continuum elasticity theory and molecular dynamics simulations.

Spatio-Temporal Transcript Profiling of Rice Roots and Shoots in Response to Phosphate Starvation and Recovery

Abstract: Using rice (Oryza sativa) as a model crop species, we performed an in-depth temporal transcriptome analysis, covering the early and late stages of Pi deprivation as well as Pi recovery in roots and shoots, using next-generation sequencing Analyses of 126 paired-end RNA sequencing libraries, spanning nine time points, provided a comprehensive overview of the dynamic responses of rice to Pi stress Differentially expressed genes were grouped into eight sets based on their responses to Pi starvation and recovery, enabling the complex signaling pathways involved in Pi homeostasis to be untangled A reference annotation-based transcript assembly was also generated, identifying 438 unannotated loci that were differentially expressed under Pi starvation Several genes also showed induction of unannotated splice isoforms under Pi starvation Among these, PHOSPHATE2 (PHO2), a key regulator of Pi homeostasis, displayed a Pi starvation–induced isoform, which was associated with increased translation activity In addition, microRNA (miRNA) expression profiles after long-term Pi starvation in roots and shoots were assessed, identifying 20 miRNA families that were not previously associated with Pi starvation, such as miR6250 In this article, we present a comprehensive spatio-temporal transcriptome analysis of plant responses to Pi stress, revealing a large number of potential key regulators of Pi homeostasis in plants

Face-to-face interventions for informing or educating parents about early childhood vaccination

Abstract: Background Childhood vaccination (also described as immunisation) is an important and effective way to reduce childhood illness and death. However, there are many children who do not receive the recommended vaccines because their parents do not know why vaccination is important, do not understand how, where or when to get their children vaccinated, disagree with vaccination as a public health measure, or have concerns about vaccine safety. Face to face interventions to inform or educate parents about routine childhood vaccination may improve vaccination rates and parental knowledge or understanding of vaccination. Such interventions may describe or explain the practical and logistical factors associated with vaccination, and enable parents to understand the meaning and relevance of vaccination for their family or community. Objectives To assess the effects of face to face interventions for informing or educating parents about early childhood vaccination on immunisation uptake and parental knowledge. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7); MEDLINE (OvidSP) (1946 to July 2012); EMBASE + Embase Classic (OvidSP) (1947 to July 2012); CINAHL (EbscoHOST) (1981 to July 2012); PsycINFO (OvidSP) (1806 to July 2012); Global Health (CAB) (1910 to July 2012); Global Health Library (WHO) (searched July 2012); Google Scholar (searched September 2012), ISI Web of Science (searched September 2012) and reference lists of relevant articles. We searched for ongoing trials in The International Clinical Trials Registry Platform (ICTRP) (searched August 2012) and for grey literature in The Grey Literature Report and OpenGrey (searched August 2012). We also contacted authors of included studies and experts in the field. There were no language or date restrictions. Selection criteria Randomised controlled trials (RCTs) and cluster RCTs evaluating the effects of face to face interventions delivered to individual parents or groups of parents to inform or educate about early childhood vaccination, compared with control or with another face to face intervention. Early childhood vaccines are all recommended routine childhood vaccines outlined by the World Health Organization, with the exception of human papillomavirus vaccine (HPV) which is delivered to adolescents. Data collection and analysis Two authors independently reviewed database search results for inclusion. Grey literature searches were conducted and reviewed by a single author. Two authors independently extracted data and assessed the risk of bias of included studies. We contacted study authors for additional information. Main results We included six RCTs and one cluster RCT involving a total of 2978 participants. Three studies were conducted in low- or middle-income countries and four were conducted in high-income countries. The cluster RCT did not contribute usable data to the review. The interventions comprised a mix of single-session and multi-session strategies. The quality of the evidence for each outcome was low to very low and the studies were at moderate risk of bias overall. All these trials compared face to face interventions directed to individual parents with control. The three studies assessing the effect of a single-session intervention on immunisation status could not be pooled due to high heterogeneity. The overall result is uncertain because the individual study results ranged from no evidence of effect to a significant increase in immunisation. Two studies assessed the effect of a multi-session intervention on immunisation status. These studies were also not pooled due to heterogeneity and the result was very uncertain, ranging from a non-significant decrease in immunisation to no evidence of effect. The two studies assessing the effect of a face to face intervention on knowledge or understanding of vaccination were very uncertain and were not pooled as data from one study were skewed. However, neither study showed evidence of an effect on knowledge scores in the intervention group. Only one study measured the cost of a case management intervention. The estimated additional cost per fully immunised child for the intervention was approximately eight times higher than usual care. The review also considered the following secondary outcomes: intention to vaccinate child, parent experience of intervention, and adverse effects. No adverse effects related to the intervention were measured by any of the included studies, and there were no data on the other outcomes of interest. Authors' conclusions The limited evidence available is low quality and suggests that face to face interventions to inform or educate parents about childhood vaccination have little to no impact on immunisation status, or knowledge or understanding of vaccination. There is insufficient evidence to comment on the cost of implementing the intervention, parent intention to vaccinate, parent experience of the intervention, or adverse effects. Given the apparently limited effect of such interventions, it may be feasible and appropriate to incorporate communication about vaccination into a healthcare encounter, rather than conduct it as a separate activity.

Consumer‐providers of care for adult clients of statutory mental health services

Abstract: Background In mental health services, the past several decades has seen a slow but steady trend towards employment of past or present consumers of the service to work alongside mental health professionals in providing services. However the effects of this employment on clients (service recipients) and services has remained unclear. We conducted a systematic review of randomised trials assessing the effects of employing consumers of mental health services as providers of statutory mental health services to clients. In this review this role is called 'consumer-provider' and the term 'statutory mental health services' refers to public services, those required by statute or law, or public services involving statutory duties. The consumer-provider's role can encompass peer support, coaching, advocacy, case management or outreach, crisis worker or assertive community treatment worker, or providing social support programmes. Objectives To assess the effects of employing current or past adult consumers of mental health services as providers of statutory mental health services. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2012, Issue 3), MEDLINE (OvidSP) (1950 to March 2012), EMBASE (OvidSP) (1988 to March 2012), PsycINFO (OvidSP) (1806 to March 2012), CINAHL (EBSCOhost) (1981 to March 2009), Current Contents (OvidSP) (1993 to March 2012), and reference lists of relevant articles. Selection criteria Randomised controlled trials of current or past consumers of mental health services employed as providers ('consumer-providers') in statutory mental health services, comparing either: 1) consumers versus professionals employed to do the same role within a mental health service, or 2) mental health services with and without consumer-providers as an adjunct to the service. Data collection and analysis Two review authors independently selected studies and extracted data. We contacted trialists for additional information. We conducted analyses using a random-effects model, pooling studies that measured the same outcome to provide a summary estimate of the effect across studies. We describe findings for each outcome in the text of the review with considerations of the potential impact of bias and the clinical importance of results, with input from a clinical expert. Main results We included 11 randomised controlled trials involving 2796 people. The quality of these studies was moderate to low, with most of the studies at unclear risk of bias in terms of random sequence generation and allocation concealment, and high risk of bias for blinded outcome assessment and selective outcome reporting. Five trials involving 581 people compared consumer-providers to professionals in similar roles within mental health services (case management roles (4 trials), facilitating group therapy (1 trial)). There were no significant differences in client quality of life (mean difference (MD) -0.30, 95% confidence interval (CI) -0.80 to 0.20); depression (data not pooled), general mental health symptoms (standardised mean difference (SMD) -0.24, 95% CI -0.52 to 0.05); client satisfaction with treatment (SMD -0.22, 95% CI -0.69 to 0.25), client or professional ratings of client-manager relationship; use of mental health services, hospital admissions and length of stay; or attrition (risk ratio 0.80, 95% CI 0.58 to 1.09) between mental health teams involving consumer-providers or professional staff in similar roles. There was a small reduction in crisis and emergency service use for clients receiving care involving consumer-providers (SMD -0.34 (95%CI -0.60 to -0.07). Past or present consumers who provided mental health services did so differently than professionals; they spent more time face-to-face with clients, and less time in the office, on the telephone, with clients' friends and family, or at provider agencies. Six trials involving 2215 people compared mental health services with or without the addition of consumer-providers. There were no significant differences in psychosocial outcomes (quality of life, empowerment, function, social relations), client satisfaction with service provision (SMD 0.76, 95% CI -0.59 to 2.10) and with staff (SMD 0.18, 95% CI -0.43 to 0.79), attendance rates (SMD 0.52 (95% CI -0.07 to 1.11), hospital admissions and length of stay, or attrition (risk ratio 1.29, 95% CI 0.72 to 2.31) between groups with consumer-providers as an adjunct to professional-led care and those receiving usual care from health professionals alone. One study found a small difference favouring the intervention group for both client and staff ratings of clients' needs having been met, although detection bias may have affected the latter. None of the six studies in this comparison reported client mental health outcomes. No studies in either comparison group reported data on adverse outcomes for clients, or the financial costs of service provision. Authors' conclusions Involving consumer-providers in mental health teams results in psychosocial, mental health symptom and service use outcomes for clients that were no better or worse than those achieved by professionals employed in similar roles, particularly for case management services. There is low quality evidence that involving consumer-providers in mental health teams results in a small reduction in clients' use of crisis or emergency services. The nature of the consumer-providers' involvement differs compared to professionals, as do the resources required to support their involvement. The overall quality of the evidence is moderate to low. There is no evidence of harm associated with involving consumer-providers in mental health teams. Future randomised controlled trials of consumer-providers in mental health services should minimise bias through the use of adequate randomisation and concealment of allocation, blinding of outcome assessment where possible, the comprehensive reporting of outcome data, and the avoidance of contamination between treatment groups. Researchers should adhere to SPIRIT and CONSORT reporting standards for clinical trials. Future trials should further evaluate standardised measures of clients' mental health, adverse outcomes for clients, the potential benefits and harms to the consumer-providers themselves (including need to return to treatment), and the financial costs of the intervention. They should utilise consistent, validated measurement tools and include a clear description of the consumer-provider role (eg specific tasks, responsibilities and expected deliverables of the role) and relevant training for the role so that it can be readily implemented. The weight of evidence being strongly based in the United States, future research should be located in diverse settings including in low- and middle-income countries.