Which components of heart failure programs are effective? A meta-analysis of the outcomes of structured telephone support or telemonitoring as the primary component of heart failure management in 9,560 patients (Abridged Cochrane Review)

Aims--Telemonitoring (TM) and structured telephone support (STS) have the potential to deliver specialised management to more patients with chronic heart failure (CHF), but their efficacy is still to be proven. Objectives To review randomised controlled trials (RCTs) of TM or STS on all- cause mortality and all-cause and CHF-related hospitalisations in patients with CHF, as a non-invasive remote model of specialised disease-management intervention.--Methods and Results--Data sources:We searched 15 electronic databases and hand-searched bibliographies of relevant studies, systematic reviews, and meeting abstracts. Two reviewers independently extracted all data. Study eligibility and participants: We included any randomised controlled trials (RCT) comparing TM or STS to usual care of patients with CHF. Studies that included intensified management with additional home or clinic visits were excluded. Synthesis: Primary outcomes (mortality and hospitalisations) were analysed; secondary outcomes (cost, length of stay, quality of life) were tabulated.--Results: Thirty RCTs of STS and TM were identified (25 peer-reviewed publications (n=8,323) and five abstracts (n=1,482)). Of the 25 peer-reviewed studies, 11 evaluated TM (2,710 participants), 16 evaluated STS (5,613 participants) and two tested both interventions. TM reduced all-cause mortality (risk ratio (RR 0•66 [95% CI 0•54-0•81], p<0•0001) and STS showed similar trends (RR 0•88 [95% CI 0•76-1•01], p=0•08). Both TM (RR 0•79 [95% CI 0•67-0•94], p=0•008) and STS (RR 0•77 [95% CI 0•68-0•87], p<0•0001) reduced CHF-related hospitalisations. Both interventions improved quality of life, reduced costs, and were acceptable to patients. Improvements in prescribing, patient-knowledge and self-care, and functional class were observed.--Conclusion: TM and STS both appear effective interventions to improve outcomes in patients with CHF.

Linear stern waves in finite depth channels

This paper formulates an analytically tractable problem for the wake generated by a long flat bottom ship by considering the steady free surface flow of an inviscid, incompressible fluid emerging from beneath a semi-infinite rigid plate. The flow is considered to be irrotational and two-dimensional so that classical potential flow methods can be exploited. In addition, it is assumed that the draft of the plate is small compared to the depth of the channel. The linearised problem is solved exactly using a Fourier transform and the Wiener-Hopf technique, and it is shown that there is a family of subcritical solutions characterised by a train of sinusoidal waves on the downstream free surface. The amplitude of these waves decreases as the Froude number increases. Supercritical solutions are also obtained, but, in general, these have infinite vertical velocities at the trailing edge of the plate. Consideration of further terms in the expansions suggests a way of canceling the singularity for certain values of the Froude number.

New stress and velocity fields for highly frictional granular materials

The idealised theory for the quasi-static flow of granular materials which satisfy the Coulomb-Mohr hypothesis is considered. This theory arises in the limit that the angle of internal friction approaches $\pi/2$, and accordingly these materials may be referred to as being `highly frictional'. In this limit, the stress field for both two-dimensional and axially symmetric flows may be formulated in terms of a single nonlinear second order partial differential equation for the stress angle. To obtain an accompanying velocity field, a flow rule must be employed. Assuming the non-dilatant double-shearing flow rule, a further partial differential equation may be derived in each case, this time for the streamfunction. Using Lie symmetry methods, a complete set of group-invariant solutions is derived for both systems, and through this process new exact solutions are constructed. Only a limited number of exact solutions for gravity driven granular flows are known, so these results are potentially important in many practical applications. The problem of mass flow through a two-dimensional wedge hopper is examined as an illustration.

Multitasking information behaviour in public libraries : a survey study

Multitasking information behaviour is the human ability to handle the demands of multiple information tasks concurrently. When we multitask, we work on two or more tasks and switch between those tasks. Multitasking is the way most of us deal with the complex environment we all live in, and recent studies show that people often engage in multitasking information behaviours. Multitasking information behaviours are little understood, however, and an important area for information behaviour research. Our study investigated the multitasking information behaviours of public library users at the Brentwood and Wilkinsburg Public Libraries in Pittsburgh through diary questionnaires. Findings include that some 63.5 percent of library users engaged in multitasking information behaviours, with a mean of 2.5 topic changes and 2.8 topics per library visit. A major finding of our study is that many people in libraries are seeking information on multiple topics and are engaged in multitasking behaviours. The implications of our findings and further research are also discussed. (Contains 7 tables and 2 figures.)

New insights into Crustal Contributions to Large-volume Rhyolite Generation in the Mid-Tertiary Sierra Madre Occidental Province, Mexico, revealed by U Pb Geochronology

Voluminous (≥3·9 × 105 km3), prolonged (∼18 Myr) explosive silicic volcanism makes the mid-Tertiary Sierra Madre Occidental province of Mexico one of the largest intact silicic volcanic provinces known. Previous models have proposed an assimilation–fractional crystallization origin for the rhyolites involving closed-system fractional crystallization from crustally contaminated andesitic parental magmas, with <20% crustal contributions. The lack of isotopic variation among the lower crustal xenoliths inferred to represent the crustal contaminants and coeval Sierra Madre Occidental rhyolite and basaltic andesite to andesite volcanic rocks has constrained interpretations for larger crustal contributions. Here, we use zircon age populations as probes to assess crustal involvement in Sierra Madre Occidental silicic magmatism. Laser ablation-inductively coupled plasma-mass spectrometry analyses of zircons from rhyolitic ignimbrites from the northeastern and southwestern sectors of the province yield U–Pb ages that show significant age discrepancies of 1–4 Myr compared with previously determined K/Ar and 40Ar/39Ar ages from the same ignimbrites; the age differences are greater than the errors attributable to analytical uncertainty. Zircon xenocrysts with new overgrowths in the Late Eocene to earliest Oligocene rhyolite ignimbrites from the northeastern sector provide direct evidence for some involvement of Proterozoic crustal materials, and, potentially more importantly, the derivation of zircon from Mesozoic and Eocene age, isotopically primitive, subduction-related igneous basement. The youngest rhyolitic ignimbrites from the southwestern sector show even stronger evidence for inheritance in the age spectra, but lack old inherited zircon (i.e. Eocene or older). Instead, these Early Miocene ignimbrites are dominated by antecrystic zircons, representing >33 to ∼100% of the dated population; most antecrysts range in age between ∼20 and 32 Ma. A sub-population of the antecrystic zircons is chemically distinct in terms of their high U (>1000 ppm to 1·3 wt %) and heavy REE contents; these are not present in the Oligocene ignimbrites in the northeastern sector of the Sierra Madre Occidental. The combination of antecryst zircon U–Pb ages and chemistry suggests that much of the zircon in the youngest rhyolites was derived by remelting of partially molten to solidified igneous rocks formed during preceding phases of Sierra Madre Occidental volcanism. Strong Zr undersaturation, and estimations for very rapid dissolution rates of entrained zircons, preclude coeval mafic magmas being parental to the rhyolite magmas by a process of lower crustal assimilation followed by closed-system crystal fractionation as interpreted in previous studies of the Sierra Madre Occidental rhyolites. Mafic magmas were more probably important in providing a long-lived heat and material flux into the crust, resulting in the remelting and recycling of older crust and newly formed igneous materials related to Sierra Madre Occidental magmatism.

Petrology and geochemistry of the Quaternary Caldera-forming, Phonolitic Granadilla Eruption, Tenerife (Canary Islands)

The Granadilla eruption at 600 ka was one of the largest phonolitic explosive eruptions from the Las Cañadas volcano on Tenerife, producing a classical plinian eruptive sequence of a widespread pumice fall deposit overlain by an ignimbrite. The eruption resulted in a major phase of caldera collapse that probably destroyed the shallow-level magma chamber system. Granadilla pumices contain a diverse phenocryst assemblage of alkali feldspar + biotite + sodian diopside to aegirine–augite + titanomagnetite + ilmenite + nosean/haüyne + titanite + apatite; alkali feldspar is the dominant phenocryst and biotite is the main ferromagnesian phase. Kaersutite and partially resorbed plagioclase (oligoclase to sodic andesine) are present in some eruptive units, particularly in pumice erupted during the early plinian phase, and in the Granadilla ignimbrite at the top of the sequence. Associated with the kaersutite and plagioclase are small clots of microlitic plagioclase and kaersutite interpreted as quenched blebs of tephriphonolitic magma within the phonolite pumice. The Granadilla Member has previously been recognized as an example of reverse-then-normal compositional zonation, where the zonation is primarily expressed in terms of substantial variations in trace element abundances with limited major element variation (cryptic zonation). Evidence for cryptic zonation is also provided by the chemistry of the phenocryst phases, and corresponding changes in intensive parameters (e.g. T, f O2, f  H2O). Geothermometry estimates indicate that the main body of phonolite magma had a temperature gradient from 860 °C to ∼790 °C, with hotter magma (≥900 °C) tapped at the onset and terminal phases of the eruption. The reverse-then-normal chemical and thermal zonation reflects the initial tapping of a partially hybridized magma (mixing of phonolite and tephriphonolite), followed by the more sequential tapping of a zoned and relatively large body of highly evolved phonolite at a new vent and during the main plinian phase. This suggests that the different magma types within the main holding chamber could have been laterally juxtaposed, as well as in a density-stratified arrangement. Correlations between the presence of mixed phenocryst populations (i.e. presence of plagioclase and kaersutite) and coarser pumice fall layers suggest that increased eruption vigour led to the tapping of hybridized and/or less evolved magma probably from greater depths in the chamber. New oxygen isotope data for glass and mineral separates preclude syn-eruptive interaction between the vesiculating magma and hydrothermal fluids as the cause of the Sr isotope disequilibrium identified previously for the deposit. Enrichment in radiogenic Sr in the pumice glass has more likely been due to low-temperature exchange with meteoric water that was enriched in 87Sr by sea spray, which may be a common process affecting porous and glassy pyroclastic deposits on oceanic islands.

Indigeneity and the judicial decision to imprison : a study of Western Australia’s higher courts

Internationally, sentencing research has largely neglected the impact of Indigeneity on sentencing outcomes. Using data from Western Australia’s higher courts for the years 2003–05, we investigate the direct and interactive effects of Indigenous status on the judicial decision to imprison. Unlike prior research on race/ethnicity in which minority offenders are often found to be more harshly treated by sentencing courts, we find that Indigenous status has no direct effect on the decision to imprison,after adjusting for other sentencing factors (especially past and current criminality).However, there are sub-group differences: Indigenous males are more likely to receive a prison sentence compared to non-Indigenous females. We draw on the focal concerns perspective of judicial decision making in interpreting our findings.

Measurement of the net environmental benefit of offsetting in Queensland

The process of offsetting land against unavoidable disturbance of development sites in Queensland will benefit from a method that allows the best possible selection to be made of alternative lands. With site selection now advocated through a combination of Regional Ecosystem and Land Capability classifications state-wide, a case study has determined methods of assessing the functional lift – that is, measures of net environmental gain – of such action. Outcomes with potentially high functional lift are determined, that offer promise not only for endangered ecosystems but also for managing adjacent conservation reserves.

Brief motivational interviewing for depression and anxiety

Motivational interviewing (MI)can be applied as a brief, low intensity (LI) intervention of 1-4 individualised sessions (typically 45-60 minutes in duration), including screening, assessment feedback, and psycho-education. MI is a client-centred, directive therapeutic style that enhances readiness for change by helping clients explore and resolve ambivalence (Miller and Rollnick 2002). A summary of the key components of brief MI interventions is provided in Table 16.1. There is a well-established evidence base for MI in the treatment of substance misuse (particularly alcohol misuse; Moyer et al. 2002), as well as a growing evidence for the use of MI in the treatment of other mental disorders (e.g. depression, PTSD, OCD), as well as suicidality and physical health problems (Hettema et al. 2005). Brief MI intervention can be delivered as a standalone treatment or as a motivational prelude to pharmacological and/or other psychological treatments (Hettema et al. 2005). MI has been used as an accompaniment to cognitive behavioural therapy (CBT) in the treatment of both depression and anxiety for resolving ambivalence about change and developing strategies for responding to resistance (e.g. treatment attendance, homework/medication compliance; Arkowitz et al. 2008a, 2008b). This chapter will describe how to apply brief MI interventions to the treatment of depression and anxiety as applied to the case of Megan (see Box 16.1) along with some of the challenges and potential solutions to applying MI in practice.

A DRD2 polymorphism predicts PANSS score variability in schizophrenia patients treated with antipsychotics

Antipsychotic medications act as either antagonists or partial agonists of the dopamine D2 receptor (DRD2) and antipsychotic drugs vary widely in their binding affinity for the D2 receptor (Kapur and Seeman, 2000). The DRD2 957CNT (rs6277) polymorphism has previously been associated with schizophrenia (Lawford et al., 2005) and the T-allele of the 957CNT polymorphism is associated with reduced mRNA stability and synthesis of the dopamine D2 receptor (Duan et al., 2003). The aim of the study was to determine if the rs6277 polymorphism predicts some of the variability of positive and negative symptoms observed in schizophrenia patients being treated with antipsychotic medication.

Spatiotemporal investigations of DNA damage repair using microbeams

Cellular response to radiation damage is made by a complex network of pathways and feedback loops whose spatiotemporal organisation is still unclear despite its decisive role in determining the fate of the damaged cell. Revealing the dynamic sequence of the repair proteins is therefore critical in understanding how the DNA repair mechanisms work. There are also still open questions regarding the possible movement of damaged chromatin domains and its role as trigger for lesion recognition and signalling in the DNA repair context. The single-cell approach and the high spatial resolution offered by microbeams provide the perfect tool to study and quantify the dynamic processes associated with the induction and repair of DNA damage. We have followed the development of radiation-induced foci for three DNA damage markers (i.e. γ-H2AX, 53BP1 and hSSB1) using normal fibroblasts (AG01522), human breast adenocarcinoma cells (MCF7) and human fibrosarcoma cells (HT1080) stably transfected with yellow fluorescent protein fusion proteins following irradiation with the QUB X-ray microbeam (carbon X-rays <2 µm spot). The size and intensity of the foci has been analysed as a function of dose and time post-irradiation to investigate the dynamics of the above-mentioned DNA repair processes and monitor the remodelling of chromatin structure that the cell undergoes to deal with DNA damage.

Physical and functional interaction of the archaeal single-stranded DNA-binding protein SSB with RNA polymerase

Archaeal transcription utilizes a complex multisubunit RNA polymerase and the basal transcription factors TBP and TF(II)B, closely resembling its eukaryal counterpart. We have uncovered a tight physical and functional interaction between RNA polymerase and the single-stranded DNA-binding protein SSB in Sulfolobus solfataricus. SSB stimulates transcription from promoters in vitro under TBP-limiting conditions and supports transcription in the absence of TBP. SSB also rescues transcription from repression by reconstituted chromatin. We demonstrate the potential for promoter melting by SSB, suggesting a plausible basis for the stimulation of transcription. This stimulation requires both the single-stranded DNA-binding domain and the acidic C-terminal tail of the SSB. The tail forms a stable interaction with RNA polymerase. These data reveal an unexpected role for single-stranded DNA-binding proteins in transcription in archaea.

Substrate recognition and catalysis by the Holliday junction resolving enzyme Hje

Two archaeal Holliday junction resolving enzymes, Holliday junction cleavage (Hjc) and Holliday junction endonuclease (Hje), have been characterized. Both are members of a nuclease superfamily that includes the type II restriction enzymes, although their DNA cleaving activity is highly specific for four-way junction structure and not nucleic acid sequence. Despite 28% sequence identity, Hje and Hjc cleave junctions with distinct cutting patterns—they cut different strands of a four-way junction, at different distances from the junction centre. We report the high-resolution crystal structure of Hje from Sulfolobus solfataricus. The structure provides a basis to explain the differences in substrate specificity of Hje and Hjc, which result from changes in dimer organization, and suggests a viral origin for the Hje gene. Structural and biochemical data support the modelling of an Hje:DNA junction complex, highlighting a flexible loop that interacts intimately with the junction centre. A highly conserved serine residue on this loop is shown to be essential for the enzyme's activity, suggesting a novel variation of the nuclease active site. The loop may act as a conformational switch, ensuring that the active site is completed only on binding a four-way junction, thus explaining the exquisite specificity of these enzymes.

hSSB1 interacts directly with the MRN complex stimulating its recruitment to DNA double-strand breaks and its endo-nuclease activity

hSSB1 is a recently discovered single-stranded DNA binding protein that is essential for efficient repair of DNA double-strand breaks (DSBs) by the homologous recombination pathway. hSSB1 is required for the efficient recruitment of the MRN complex to sites of DSBs and for the efficient initiation of ATM dependent signalling. Here we explore the interplay between hSSB1 and MRN. We demonstrate that hSSB1 binds directly to NBS1, a component of the MRN complex, in a DNA damage independent manner. Consistent with the direct interaction, we observe that hSSB1 greatly stimulates the endo-nuclease activity of the MRN complex, a process that requires the C-terminal tail of hSSB1. Interestingly, analysis of two point mutations in NBS1, associated with Nijmegen breakage syndrome, revealed weaker binding to hSSB1, suggesting a possible disease mechanism.

hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex

hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).