A Multi-wavelength View of the TeV Blazar Markarian 421: Correlated Variability, Flaring, and Spectral Evolution

We report results from a multi-wavelength monitoring campaign on Mrk 421 over the period of 2003-2004. The source was observed simultaneously at TeV and X-ray energies, with supporting observations frequently carried out at optical and radio wavelengths. The large amount of simultaneous data has allowed us to examine the variability of Mrk 421 in detail. The variabilities are generally correlated between the X-ray and gamma-ray bands, although the correlation appears to be fairly loose. The light curves show the presence of flares with varying amplitudes on a wide range of timescales both at X-ray and TeV energies. Of particular interest is the presence of TeV flares that have no coincident counterparts at longer wavelengths, because the phenomenon seems difficult to understand in the context of the proposed emission models for TeV blazars. We have also found that the TeV flux reached its peak days before the X-ray flux during a giant flare in 2004. Such a difference in the development of the flare presents a further challenge to the emission models. Mrk 421 varied much less at optical and radio wavelengths. Surprisingly, the normalized variability amplitude in optical seems to be comparable to that in radio, perhaps suggesting the presence of different populations of emitting electrons in the jet. The spectral energy distribution (SED) of Mrk 421 is seen to vary with flux, with the two characteristic peaks moving toward higher energies at higher fluxes. We have failed to fit the measured SEDs with a one-zone SSC model; introducing additional zones greatly improves the fits. We have derived constraints on the physical properties of the X-ray/gamma-ray flaring regions from the observed variability (and SED) of the source. The implications of the results are discussed. (Abridged)Comment: 32 pages, 12 figures, to appear in Ap

The First VERITAS Telescope

The first atmospheric Cherenkov telescope of VERITAS (the Very Energetic Radiation Imaging Telescope Array System) has been in operation since February 2005. We present here a technical description of the instrument and a summary of its performance. The calibration methods are described, along with the results of Monte Carlo simulations of the telescope and comparisons between real and simulated data. The analysis of TeV $\gamma$-ray observations of the Crab Nebula, including the reconstructed energy spectrum, is shown to give results consistent with earlier measurements. The telescope is operating as expected and has met or exceeded all design specifications.Comment: Accepted by Astroparticle Physic

A Search for TeV Gamma-Ray Emission from High-Peaked Flat Spectrum Radio Quasars Using the Whipple Air-Cherenkov Telescope

Blazars have traditionally been separated into two broad categories based upon their optical emission characteristics; BL Lacs, with faint or no emission lines, and flat spectrum radio quasars (FSRQs) with prominent, broad emission lines. The spectral energy distribution of FSRQs has generally been thought of as being more akin to the low-peaked BL Lacs, which exhibit a peak in the infrared region of the spectrum, as opposed to high-peaked BL Lacs (HBLs), which exhibit a peak in UV/X-ray region of the spectrum. All blazars currently confirmed as sources of TeV emission are HBLs. Recent surveys have found several FSRQs exhibiting spectral properties similar to HBLs, particularly the synchrotron peak frequency. These objects are potential sources of TeV emission according to several models of blazar jet emission and blazar evolution. Measurements of TeV flux or upper limits could impact existing theories explaining the links between different blazar types and could have a significant impact on our understanding of the nature of objects that are capable of TeV emission. In particular, the presence (or absence) of TeV emission from FSRQs could confirm (or cast doubt upon) recent evolutionary models that expect intermediate objects in a transitionary state between FSRQ and BL Lac. The Whipple 10 meter imaging air-Cherenkov gamma-ray telescope is well suited for TeV gamma-ray observations. Using the Whipple telescope, we have taken data on a small selection of nearby(z<0.1 in most cases), high-peaked FSRQs. Although one of the objects, B2 0321+33, showed marginal evidence of flaring, no significant emission was detected. The implications of this paucity of emission and the derived upper limits are discussed.Comment: accepted for publication in Astrophysical Journa

The common PKD1 p.(Ile3167Phe) variant is hypomorphic and associated with very early onset, biallelic polycystic kidney disease

Biallelic PKD1 variants, including hypomorphic variants, can cause very early onset polycystic kidney disease (VEO-PKD). A family with unexplained recurrent VEO-PKD and neonatal demise in one dizygotic twin was referred for clinical testing. Further individuals with the putative hypomorphic PKD1 variant, p.(Ile3167Phe), were identified from the UK 100,000 genomes project (100 K), UK Biobank (UKBB), and a review of the literature. We identified a likely pathogenic PKD1 missense paternal variant and the putative hypomorphic PKD1 variant from the unaffected mother in the deceased twin but only the paternal PKD1 variant in the surviving dizygotic twin. Analysis of 100 K cases identified a second family with two siblings with similar biallelic inheritance who presented at birth with VEO-PKD and reached kidney failure in their teens unlike other affected relatives. Finally, a survey of 618 UKBB cases confirmed that adult patients monoallelic for PKD1 p.(Ile3167Phe) had normal kidney function. Our data reveals that p.(Ile3167Phe) is the second most common PKD1 hypomorphic variant identified and is neutral in heterozygosity but is associated with VEO-PKD when inherited in trans with a pathogenic PKD1 variant. Care should be taken to ensure that it is not automatically filtered from sequence data for VEO cases

Communication of cancer screening results by letter, telephone or in person: A mixed methods systematic review of the effect on attendee anxiety, understanding and preferences

Attending and receiving a result from screening can be an anxious process. Using an appropriate method to deliver screening results could improve communication and reduce negative outcomes for screening attendees. Screening programmes are increasingly communicating results by letter or telephone rather than in-person. We investigated the impact of communication methods on attendees. We systematically reviewed the literature on the communication methods used to deliver results in cancer screening programmes for women, focusing on screening attendee anxiety, understanding of results and preferences for results communication. We included qualitative and quantitative research. We searched MEDLINE, PsycINFO, CINAHL, Cochrane Library and Embase. Results were analysed using framework synthesis. 10,558 papers were identified with seven studies meeting the inclusion criteria. Several key ideas emerged from the synthesis including speed, accuracy of results, visual support, ability to ask questions, privacy of results location and managing expectations. Verbal communication methods (telephone and in-person) were preferred and facilitated greater understanding than written methods, although there was considerable variability in attendee preferences. Findings for anxiety were mixed, with no clear consensus on which method of communication might minimise attendee anxiety. The low number of identified studies and generally low quality evidence suggest we do not know the most appropriate communication methods in the delivery of cancer screening results. More research is needed to directly compare methods of results communication, focusing on what impact each method may have on screening attendees

Healthcare professionals' perspectives on enrolled nurses, practical nurses and other second-level nursing roles: A systematic review and thematic synthesis.

BACKGROUND: Significant workforce shortages and economic pressures have led to the expanded scope and reintroduction of new roles for second-level nurses in many Organization for Economic Co-operation and Development countries. Given this, there is a need to understand the emic and etic perspectives of second-level nurses, to ensure collaborative teamwork and safe patient care. OBJECTIVE: This review aimed to systematically identify, appraise, and synthesize qualitative research evidence on healthcare professionals' perspectives on second-level nursing roles in the healthcare workforce. These findings inform recommendations that would influence the development and implementation of these roles in healthcare organisations. DESIGN: A systematic review and thematic synthesis of qualitative research was conducted. Six databases were systematically searched and forward and backwards searching completed. Included studies focused on healthcare professionals' perspectives (including views of second-level nurses themselves) on second-level nursing roles. All included articles were from Organization for Economic Co-operation and Development countries. The Critical Appraisal Skills Programme checklist for qualitative research was used to assess the evidence quality. The results section of each included article was coded and descriptive themes were developed. An interpretative and iterative process led to the final analytic themes. FINDINGS: Twenty-six qualitative studies were identified from five countries over 26 years. Four analytic themes were identified: undifferentiated role; efficient but limited; subordinated task-doers; and broadening scope and strengthened identity. The synthesis demonstrated dichotomies wherein some second-level nursing roles were devalued, and others had increasing scope and responsibility. Role and boundary confusion was evident and had not decreased over time. Hierarchies in nursing practice underlined the split between critical thinking and hands-on approaches to care which, in some cases, debased the second-level nursing role because of its association with practical hands-on care. CONCLUSIONS: The analytic themes in this synthesis suggest that second-level nurses have faced the same issues over decades with little change. Perceptions of second-level nursing roles are primarily influenced by meso (organisational level) factors and micro (individual, behavioural) factors. The synthesis concludes that a cultural shift in valuing the hands-on care provided by second-level nursing is necessary, along with systems-level shift that clarifies the role of second-level nursing within healthcare teams to enhance collaborative practice. Further research should attend to macro-level influences on perceptions of second-level nurses, the work they do, and how this is valued or institutionally embedded. Tweetable abstract: Healthcare professionals' perspectives on second-level nursing roles: a systematic review and thematic synthesis

Young patients', parents', and survivors' communication preferences in paediatric oncology: Results of online focus groups

Contains fulltext : 51596.pdf ( ) (Open Access)BACKGROUND: Guidelines in paediatric oncology encourage health care providers to share relevant information with young patients and parents to enable their active participation in decision making. It is not clear to what extent this mirrors patients' and parents' preferences. This study investigated communication preferences of childhood cancer patients, parents, and survivors of childhood cancer. METHODS: Communication preferences were examined by means of online focus groups. Seven patients (aged 8-17), 11 parents, and 18 survivors (aged 8-17 at diagnosis) participated. Recruitment took place by consecutive inclusion in two Dutch university oncological wards. Questions concerned preferences regarding interpersonal relationships, information exchange and participation in decision making. RESULTS: Participants expressed detailed and multi-faceted views regarding their needs and preferences in communication in paediatric oncology. They agreed on the importance of several interpersonal and informational aspects of communication, such as honesty, support, and the need to be fully informed. Participants generally preferred a collaborative role in medical decision making. Differences in views were found regarding the desirability of the patient's presence during consultations. Patients differed in their satisfaction with their parents' role as managers of the communication. CONCLUSION: Young patients' preferences mainly concur with current guidelines of providing them with medical information and enabling their participation in medical decision making. Still, some variation in preferences was found, which faces health care providers with the task of balancing between the sometimes conflicting preferences of young cancer patients and their parents

TeV Gamma-Ray Observations of the Perseus and Abell 2029 Galaxy Clusters

Galaxy clusters might be sources of TeV gamma rays emitted by high-energy protons and electrons accelerated by large scale structure formation shocks, galactic winds, or active galactic nuclei. Furthermore, gamma rays may be produced in dark matter particle annihilation processes at the cluster cores. We report on observations of the galaxy clusters Perseus and Abell 2029 using the 10 m Whipple Cherenkov telescope during the 2003-2004 and 2004-2005 observing seasons. We apply a two-dimensional analysis technique to scrutinize the clusters for TeV emission. In this paper we first determine flux upper limits on TeV gamma-ray emission from point sources within the clusters. Second, we derive upper limits on the extended cluster emission. We subsequently compare the flux upper limits with EGRET upper limits at 100 MeV and theoretical models. Assuming that the gamma-ray surface brightness profile mimics that of the thermal X-ray emission and that the spectrum of cluster cosmic rays extends all the way from thermal energies to multi-TeV energies with a differential spectral index of -2.1, our results imply that the cosmic ray proton energy density is less than 7.9% of the thermal energy density for the Perseus cluster.Comment: Accepted for publication in the Astrophysical Journa

NatF Contributes to an Evolutionary Shift in Protein N-Terminal Acetylation and Is Important for Normal Chromosome Segregation

N-terminal acetylation (N-Ac) is a highly abundant eukaryotic protein modification. Proteomics revealed a significant increase in the occurrence of N-Ac from lower to higher eukaryotes, but evidence explaining the underlying molecular mechanism(s) is currently lacking. We first analysed protein N-termini and their acetylation degrees, suggesting that evolution of substrates is not a major cause for the evolutionary shift in N-Ac. Further, we investigated the presence of putative N-terminal acetyltransferases (NATs) in higher eukaryotes. The purified recombinant human and Drosophila homologues of a novel NAT candidate was subjected to in vitro peptide library acetylation assays. This provided evidence for its NAT activity targeting Met-Lys- and other Met-starting protein N-termini, and the enzyme was termed Naa60p and its activity NatF. Its in vivo activity was investigated by ectopically expressing human Naa60p in yeast followed by N-terminal COFRADIC analyses. hNaa60p acetylated distinct Met-starting yeast protein N-termini and increased general acetylation levels, thereby altering yeast in vivo acetylation patterns towards those of higher eukaryotes. Further, its activity in human cells was verified by overexpression and knockdown of hNAA60 followed by N-terminal COFRADIC. NatF's cellular impact was demonstrated in Drosophila cells where NAA60 knockdown induced chromosomal segregation defects. In summary, our study revealed a novel major protein modifier contributing to the evolution of N-Ac, redundancy among NATs, and an essential regulator of normal chromosome segregation. With the characterization of NatF, the co-translational N-Ac machinery appears complete since all the major substrate groups in eukaryotes are accounted for

Parental health limitations, caregiving and loneliness among women with widowed parents: longitudinal eveidence from France

We investigate how daughters’ feelings of loneliness are impacted when widowed parents develop health limitations, and when daughters take on personal care tasks in response. Using longitudinal data from daughters of widowed parents drawn from the French Family and Intergenerational Relationships Study (ERFI, 1485 observations nested in 557 daughters), we assess (a) whether health limitations of widowed parents are associated with daughters’ feelings of loneliness regardless of whether or not daughters provide personal care and (b) whether there is an effect of care provision on loneliness that cannot be explained by parental health limitations. Fixed effect regression analyses show that widowed parents’ health limitations were associated with raised feelings of loneliness among their daughters. No significant additional effect of providing personal care to a widowed parent was found. Prior research on the impact of health limitations of older parents on the lives of their adult–children has focused mostly on issues related to informal caregiving. Our findings suggest that more attention to the psychosocial impact of parental health limitations—net of actual caregiving—on adult children’s lives is warranted