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Previous genetic association studies have failed to identify loci robustly associated with sepsis, and there have been no published genetic association studies or polygenic risk score analyses of patients with septic shock, despite evidence suggesting genetic factors may be involved. We systematically collected genotype and clinical outcome data in the context of a randomized controlled trial from patients with septic shock to enrich the presence of disease-associated genetic variants. We performed genomewide association studies of susceptibility and mortality in septic shock using 493 patients with septic shock and 2442 population controls, and polygenic risk score analysis to assess genetic overlap between septic shock risk/mortality with clinically relevant traits. One variant, rs9489328, located in AL589740.1 noncoding RNA, was significantly associated with septic shock (p = 1.05 × 10–10); however, it is likely a false-positive. We were unable to replicate variants previously reported to be associated (p < 1.00 × 10–6 in previous scans) with susceptibility to and mortality from sepsis. Polygenic risk scores for hematocrit and granulocyte count were negatively associated with 28-day mortality (p = 3.04 × 10–3; p = 2.29 × 10–3), and scores for C-reactive protein levels were positively associated with susceptibility to septic shock (p = 1.44 × 10–3). Results suggest that common variants of large effect do not influence septic shock susceptibility, mortality and resolution; however, genetic predispositions to clinically relevant traits are significantly associated with increased susceptibility and mortality in septic individuals.
This article reports on an evaluation of the Keeping Children Safe parent education programme run in Central West New South Wales. The programme, conducted since 2004, and continuing today, primarily targets parents of children at risk and other vulnerable and disadvantaged families. The evaluation covers a 13-year period, from the first group held in May 2004 to February 2017. From the beginning, the authors strategically endeavoured to recruit and retain parents from the target group. Findings from the literature indicate that this group is difficult to engage and retain in parent education groups. Parents targeted for the groups in this study were generally not receiving parent education elsewhere. Using mixed methods, the facilitators have continuously evaluated the programme in terms of attendance rates, process and impact. The results of these evaluations show successful recruitment and retention of participants from the target group over the 13 years of the evaluation reporting period and indicate that the programme’s immediate impact on participants has been favourable. The findings complement other programme evaluations focusing on recruitment and retention to programmes in the child protection context and on hard-to-reach clients. The authors also argue the importance of education for parents about child abuse and neglect.
OBJECTIVES/GOALS: Primary graft dysfunction (PGD) is acute lung injury in the first three days after lung transplant. Patients that experience PGD have increased mortality and an increased risk of chronic lung allograft dysfunction. The pathogenesis is thought to be an ischemia-reperfusion injury but is incompletely understood and there are no specific therapies. We investigated the role of the microbiome in PGD and associations with inflammation and markers of aspiration. METHODS/STUDY POPULATION: We collected airway lavage samples from lung transplant donors before procurement and recipients after reperfusion. We extracted DNA, amplified the bacterial 16S rRNA gene, and sequenced on the Illumina MiSeq platform. QIIME2 and Deblur were used for bioinformatic analysis. R packages were used for downstream analysis and visualizations. The host response was quantified using the Milipore 41-plex Luminex and an ELISA for pepsin. Clinical data was collected by the Penn Lung Transplant Outcomes Group. PGD was assessed by degree of hypoxemia and chest X-ray findings in the 72 hours after transplant. RESULTS/ANTICIPATED RESULTS: There was no significant difference in alpha diversity (Shannon index, p = 0.51), biomass (via comparison of 16S amplicon PicoGreen, p = 0.6), or beta diversity (Weighted UniFrac, p = 0.472, PERMANOVA) between subjects with PGD grade 3 (n = 36) and those that did not (n = 96). On taxonomic analysis, we found an enrichment of Prevotella in donor and recipient lungs that went on to develop PGD (p = 0.05). To follow up this finding we measured immune response and pepsin concentrations in recipient lungs. We found elevated levels in 35/41 cytokines measured in subjects that developed PGD as well as an elevation in pepsin and a correlation between pepsin concentration and Prevotella relative abundance (Figure 1). Additionally, Prevotella relative abundance had statistically significant positive correlations with multiple cytokines such as IL-6 (Pearson’s = 0.26, p = 0.009) and eotaxin (Pearson’s = 0.24, p = 0.016). DISCUSSION/SIGNIFICANCE OF IMPACT: There is an enrichment of oral anerobes in lung allografts that eventually develop PGD. This is associated with elevated levels of pepsin and markers of inflammation. These lines of evidence suggest aspiration contributes to priming the allograft for PGD.
Although there is some evidence that duration of untreated psychosis (DUP) is geographically stable, few have examined whether the phenomenon is temporally stable. We examined DUP in two cohorts within two discrete time periods (1995–1999 and 2003–2005) spanning a decade in the same geographically defined community psychiatric service with no early intervention programme. Patients were diagnosed by Structured Clinical Interview for DSM (SCID) and we determined the DUP using the Beiser Scale. The DUP of the 240 participants did not differ significantly between study periods.
Biases in cognition such as Jumping to Conclusions (JTC) and Verbal Self-Monitoring (VSM) are thought to underlie the formation of psychotic symptoms. This prospective study in people with an At Risk Mental State (ARMS) for psychosis examined how these cognitive biases changed over time, and predicted clinical and functional outcomes. Twenty-three participants were assessed at clinical presentation and a mean of 31 months later. Performance on a JTC and VSM tasks were measured at both time points. Relationships to symptom severity, level of function and the incidence of psychotic disorder were then examined. The levels of symptoms, function and VSM all improved over time, while JTC was stable. Five participants (22%) developed a psychotic disorder during the follow-up period, but the risk of transition was not related to performance on either task at baseline, or to longitudinal changes in task performance. JTC performance correlated with symptom severity at baseline and follow-up. Similarly, performance on the two tasks was not related to the level of functioning at follow-up. Thus, while the ARMS is associated with both VSM and JTC biases, neither predict the onset of psychosis or the overall functional outcome.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Balloon aortic valvuloplasty and open surgical valvotomy are procedures to treat neonatal aortic stenosis, and there is controversy as to which method has superior outcomes.
We reviewed the records of patients at our institution since 2000 who had a balloon aortic valvuloplasty or surgical valvotomy via an open commissurotomy prior to 2 months of age.
Forty patients had balloon aortic valvuloplasty and 15 patients had surgical valvotomy via an open commissurotomy. There was no difference in post-procedure mean gradient by transthoracic echocardiogram, which were 25.8 mmHg for balloon aortic valvuloplasty and 26.2 mmHg for surgical valvotomy, p = 0.87. Post-procedure, 15% of balloon aortic valvuloplasty patients had moderate aortic insufficiency and 2.5% of patients had severe aortic insufficiency, while no surgical valvotomy patients had moderate or severe aortic insufficiency. The average number of post-procedure hospital days was 14.2 for balloon aortic valvuloplasty and 19.8 for surgical valvotomy (p = 0.52). Freedom from re-intervention was 69% for balloon aortic valvuloplasty and 67% for surgical valvotomy at 1 year, and 43% for balloon aortic valvuloplasty and 67% for surgical valvotomy at 5 years (p = 0.60).
Balloon aortic valvuloplasty and surgical valvotomy provide similar short-term reduction in valve gradient. Balloon aortic valvuloplasty has a slightly shorter but not statistically significant hospital stay. Freedom from re-intervention is similar at 1 year. At 5 years, it is slightly higher in surgical valvotomy, though not statistically different. Balloon aortic valvuloplasty had a higher incidence of significant aortic insufficiency. Long-term comparisons cannot be made given the lack of long-term follow-up with surgical valvotomy.
Chapter 1 introduced the basic ‘tools’ of performance and reward management, including key aspects of purpose and practice. In this chapter we introduce two overarching concepts of alignment that recur throughout this book: ‘strategic alignment’ and ‘psychological engagement’. The design, implementation and maintenance of effective performance and reward management systems requires simultaneous, systematic and constant attention to both of these dimensions of alignment.
‘Strategic alignment’ refers to the plans, processes and actions involved in establishing and maintaining an alignment between an organisation’s overarching purpose or intent and how it manages employee performance and reward, as well as all other aspects of people management.
This is a book about two of the core activities integral in the field of human resource management: managing employee performance and managing how employees are rewarded. As we shall see throughout the book, there is a close and complex inter-dependence between these two activities; so much so that it makes little sense to consider them in isolation from each other. Equally, while the book’s central concerns are with performance and reward practices and processes, attention is also paid throughout to recognising and analysing the interconnectedness of these and other aspects of human resource management. Performance management systems provide inputs into other HR functions such as training and employee development, as well as evaluating HR decisions such as recruitment and selection.
In this final chapter, we explore emerging trends – the new horizons – in business, technology and society with a particular focus on how these developments are influencing ideas, practice, employee experience and academic research in the field of performance and reward management. We begin with emerging trends and practices that have already begun to impact the design of performance and reward management systems and academic research in the field. We focus on three interconnected global trends that have already started to change performance and reward management practice; an impact that is very likely to increase in the years ahead. The first of these trends is the technological revolution associated with ‘Industry 4.0’; the second is the economic disruption and employment uncertainty associated with what has come to be called the ‘gig economy’; and the third is the social transformation flowing from generational change around the world.
The third edition of Managing Employee Performance and Reward: Systems, Practices and Prospects has been thoroughly revised and updated by a new four-member author team. The text introduces a new conceptual framework based on systems thinking and a dual model of strategic alignment and psychological engagement. Coverage of chapter topics provides a balance between research evidence and practice and, in this new edition, is enhanced with a more applied and technical approach. The text also includes chapters dedicated to conceptual framing, base pay and individual recognition and reward; 'reality check' breakout boxes with practical examples and current problems on each of strategic alignment, employee engagement, organisation justice and workforce diversity; and a new chapter exploring new horizons in performance and reward practice and research with a focus on the mega-trends of technological transformation under 'Industry 4.0', new economic forms and relationships arising from the 'gig' economy, and generational change.