Reducing sickness absence in Scotland - applying the lessons from a pilot NHS intervention

In May 2008 NHS Lanarkshire (NHSL) implemented a unique sickness absence management service called ‘Early Access to Support to You’ (EASY) service. The EASY service supplements existing absence policies and enables communication between the absentee and their line manager from Day 1 of absence and referral to occupational health at day 10. We analysed three sources of data and showed that the EASY service was effective in reducing sickness absence and NHSL moved from the worst performing Scottish mainland Health Board to the best in terms of sickness absence management. The service was also cost effective; the value of the hours saved comfortably exceeded the cost of the intervention

Early maternal-infant interactions in adolescent and young adult mothers

Children having children! Over a million American teenagers become pregnant every year and over half a million give birth. While ignored in the past, the problem has now become a "burning national concern." Teen parenting has been linked to various problems, including high rates of infant mortality and morbidity, social/economic risks to the family, and developmental risks to the child. This research investigated differences between 100 adolescent women and 100 young adult women expecting their first child. The subjects were interview during their third trimester of pregnancy, followed through the births of their infants, and observed interacting with their infants at 3-5 weeks post-partum. Based on the pre-partum data, a significant difference was found for knowledge about infants and infant care, with the young adult women possessing greater knowledge. The two groups did not differ on their perception of caretaking competence nor on their maternal-fetal attachment

The effects of expectancy and parenthood on observations by parents

With the move from clinical settings to the "natural" environment, parents have become mediators of behavioral change with their children. In this role, parents often serve as both experimenters and observers. The present study investigated some of the parameters of parental observations such as sex of parent, reliability, effects of expectancy, and effects of parenthood. Four sets of parents were trained on a six-category behavioral code via video tape. Parents then observed four, equivalent (equal number of positive and negative behaviors) 10-minute video tapes, each tape being a different child and a different condition. The four conditions used were: positive expectancy, negative expectancy, neutral, and own-child. Given the small amount of training in observations (one hour), the parents proved to be reliable observers — mean reliability of .79. There were no significant effects on the observational data due to sex of parent nor expectancy

The Next WHO Director-General’s Highest Priority: a Global Treaty on the Human Right to Health

Amidst the many challenges facing the next WHO Director-General, the new WHO head should find WHO’s foremost priority in its most important constitutional pillar: the right to health. The centerpiece of this endeavor should be leadership on the Framework Convention on Global Health (FCGH), the proposed global treaty based in the right to health and aimed at national and global health equity. The treaty would reform global governance for health to enhance accountability, transparency, and civil society participation and protect the right to health in trade, investment, climate change, and other international regimes, while catalyzing governments to institutionalize the right to health at community through to national levels. It would usher in a new era of global health with justice – vast improvements in health outcomes, equitably distributed. With the Framework Convention on Tobacco Control having served as a proof of concept, the FCGH would be an innovative treaty finding solutions to overcome global health failings in accountability, equality, financing, and inter-sectoral coherence. It would include a global health accountability framework, encompassing, civil society engagement, independent monitoring, and plans for redress, while catalyzing national health accountability strategies, accountability mechanisms, disaggregated data, and community participation. National health equity strategies, pro-poor pathways to universal health coverage, and robust non-discrimination provisions could elevate the voices, priorities, and ultimately power of marginalized populations. The FCGH would include a national and global health financing framework, while reaching beyond the health sector with right to health assessments, public health participation in developing international agreements, and responsibility for all sectors for improving health outcomes. The FCGH would reinvigorate WHO’s global health leadership, breathing new life into its founding principles. It could become the platform for reforming WHO as a rights-based 21st century institution, with badly-needed reforms, such as community participation, new priorities favouring social determinants of health, and a culture of transparency and accountability. The next Director-General should launch a historic effort to align national and global governance for with human rights through the FCGH, bringing the world closer to global health with justice

Undoing gender through performing the other

Following the perspective of gender as a socially constructed performance, consumer research has given light to how individuals take on, negotiate, and express a variety of gender roles. Yet the focus of research has remained on gender roles themselves, largely overlooking the underlying process of gender performativity and consumers’ engagement with it in the context of their everyday lives. Set within a performance methodology and the context of crossplay in live action role-playing games, this paper explores how individuals undo gender on a subjective level, thus becoming conscious and reflexive of gender performativity. The study suggests that individuals become active in undoing gender through engaging in direct, bodily performance of the gender other. Such performance does not challenge or ridicule norms, but pushes individuals to actively figure out for themselves how gender is performed. As a result, individuals become aware of gender performativity and become capable of actively recombining everyday performance

Evaluating sickness absence duration by musculoskeletal and mental health issues: a retrospective cohort study of Scottish healthcare workers

Objectives: Sickness absence (SA) among healthcare workers is associated with occupational and non-occupational risk factors and impacts employee health, healthcare delivery and patient health. At the same time, healthcare is one of the employment sectors with the highest rates of work-related ill health in the UK. Musculoskeletal (MSK) and mental health (MH) issues are leading causes of SA, but there is a lack of research on how certain MSK/MH conditions impact on SA duration. The study aim is to determine differences in SA duration by MH and MSK disorders in healthcare employees. Methods: Survival analyses were used to estimate SA duration due to MSK and MH problems over 6 years, and Cox’s proportional hazards models to determine the HRs of returning to work, using a bespoke Scottish health board database with over 53 000 SA events. SA duration and time to return-to-work (RTW) were estimated for employees by age, gender, job and health conditions. Results: MSK and MH conditions accounted for 27% and 6% of all SA events and 23.7% and 19.5% of all days lost, respectively. Average SA duration was 43.5 days for MSK and 53.9 days for MH conditions. For MSK conditions, employees with low back or neck pain had the fastest RTW (median P50: 7 days), whereas employees absent due to depression took the longest (P50: 54 days). The most influential sociodemographic variables affecting RTW were age, gender and job category. Conclusions: Using a unique and rich database, we found significant differences in SA duration by presenting condition in healthcare workers. MH conditions, and depression specifically, accounted for the most working days’ absence. Significant variations in duration were also observed for MSK conditions. Our findings can inform public health practitioners and healthcare managers of the most significant factors impacting MSK-related and MH-related SA to develop and implement tailored and targeted workplace interventions

Implementation of contemporary chemotherapy for patients with metastatic pancreatic ductal adenocarcinoma: a population-based analysis

Background: Positive results of randomized trials led to the introduction of FOLFIRINOX in 2012 and gemcitabine with nab-paclitaxel in 2015 for patients with metastatic pancreatic ductal adenocarcinoma. It is unknown to which extent these new chemotherapeutic regimens have been implemented in clinical practice and what the impact has been on overall survival. Material and methods: Patients diagnosed with metastatic pancreatic ductal adenocarcinoma between 2007–2016 were included from the population-based Netherlands Cancer Registry. Multilevel logistic regression and Cox regression analyses, adjusting for patient, tumor, and hospital characteristics, were used to analyze variation of chemotherapy use. Results: In total, 8726 patients were included. The use of chemotherapy increased from 31% in 2007–2011 to 37% in 2012–2016 (p <.001). Variation in the use of any chemotherapy between centers decreased (adjusted range 2007–2011: 12–67%, 2012–2016: 20–54%) whereas overall survival increased from 5.6 months to 6.4 months (p <.001) for patients treated with chemotherapy. Use of FOLFIRINOX and gemcitabine with nab-paclitaxel varied widely in 2015–2016, but both showed a more favorable overall survival compared to gemcitabine monotherapy (median 8.0 vs. 7.0 vs. 3.8 months, respectively). In the period 2015–2016, FOLFIRINOX was used in 60%, gemcitabine with nab-paclitaxel in 9.7% and gemcitabine monotherapy in 25% of patients receiving chemotherapy. Conclusion: Nationwide variation in the use of chemotherapy decreased after the implementation of FOLFIRINOX and gemcitabine with nab-paclitaxel. Still a considerable proportion of patients receives gemcitabine monotherapy. Overall survival did improve, but not clinically relevant. These results emphasize the need for a structured implementation of new chemotherapeutic regimens

Design and synthesis of novel aminoindazole-pyrrolo[2,3-b]pyridine inhibitors of IKKα that selectively perturb cellular non-canonical NF-κB signalling

The inhibitory-kappaB kinases (IKKs) IKKα and IKKβ play central roles in regulating the non-canonical and canonical NF-κB signalling pathways. Whilst the proteins that transduce the signals of each pathway have been extensively characterised, the clear dissection of the functional roles of IKKα-mediated non-canonical NF-κB signalling versus IKKβ-driven canonical signalling remains to be fully elucidated. Progress has relied upon complementary molecular and pharmacological tools; however, the lack of highly potent and selective IKKα inhibitors has limited advances. Herein, we report the development of an aminoindazole-pyrrolo[2,3-b]pyridine scaffold into a novel series of IKKα inhibitors. We demonstrate high potency and selectivity against IKKα over IKKβ in vitro and explain the structure–activity relationships using structure-based molecular modelling. We show selective target engagement with IKKα in the non-canonical NF-κB pathway for both U2OS osteosarcoma and PC-3M prostate cancer cells by employing isoform-related pharmacodynamic markers from both pathways. Two compounds (SU1261 [IKKα Ki = 10 nM; IKKβ Ki = 680 nM] and SU1349 [IKKα Ki = 16 nM; IKKβ Ki = 3352 nM]) represent the first selective and potent pharmacological tools that can be used to interrogate the different signalling functions of IKKα and IKKβ in cells. Our understanding of the regulatory role of IKKα in various inflammatory-based conditions will be advanced using these pharmacological agents

Design and Synthesis of Novel Aminoindazole-pyrrolo[2,3-b]pyridine Inhibitors of IKKα That Selectively Perturb Cellular Non-Canonical NF-κB Signalling

The inhibitory-kappaB kinases (IKKs) IKKα and IKKβ play central roles in regulating the non-canonical and canonical NF-κB signalling pathways. Whilst the proteins that transduce the signals of each pathway have been extensively characterised, the clear dissection of the functional roles of IKKα-mediated non-canonical NF-κB signalling versus IKKβ-driven canonical signalling remains to be fully elucidated. Progress has relied upon complementary molecular and pharmacological tools; however, the lack of highly potent and selective IKKα inhibitors has limited advances. Herein, we report the development of an aminoindazole-pyrrolo[2,3-b]pyridine scaffold into a novel series of IKKα inhibitors. We demonstrate high potency and selectivity against IKKα over IKKβ in vitro and explain the structure–activity relationships using structure-based molecular modelling. We show selective target engagement with IKKα in the non-canonical NF-κB pathway for both U2OS osteosarcoma and PC-3M prostate cancer cells by employing isoform-related pharmacodynamic markers from both pathways. Two compounds (SU1261 [IKKα Ki = 10 nM; IKKβ Ki = 680 nM] and SU1349 [IKKα Ki = 16 nM; IKKβ Ki = 3352 nM]) represent the first selective and potent pharmacological tools that can be used to interrogate the different signalling functions of IKKα and IKKβ in cells. Our understanding of the regulatory role of IKKα in various inflammatory-based conditions will be advanced using these pharmacological agents

Investigation of NRXN1 deletions: Clinical and molecular characterization

Deletions at 2p16.3 involving exons of NRXN1 are associated with susceptibility for autism and schizophrenia, and similar deletions have been identified in individuals with developmental delay and dysmorphic features. We have identified 34 probands with exonic NRXN1 deletions following referral for clinical microarray‐based comparative genomic hybridization. To more firmly establish the full phenotypic spectrum associated with exonic NRXN1 deletions, we report the clinical features of 27 individuals with NRXN1 deletions, who represent 23 of these 34 families. The frequency of exonic NRXN1 deletions among our postnatally diagnosed patients (0.11%) is significantly higher than the frequency among reported controls (0.02%; P  = 6.08 × 10 −7 ), supporting a role for these deletions in the development of abnormal phenotypes. Generally, most individuals with NRXN1 exonic deletions have developmental delay (particularly speech), abnormal behaviors, and mild dysmorphic features. In our cohort, autism spectrum disorders were diagnosed in 43% (10/23), and 16% (4/25) had epilepsy. The presence of NRXN1 deletions in normal parents and siblings suggests reduced penetrance and/or variable expressivity, which may be influenced by genetic, environmental, and/or stochastic factors. The pathogenicity of these deletions may also be affected by the location of the deletion within the gene. Counseling should appropriately represent this spectrum of possibilities when discussing recurrence risks or expectations for a child found to have a deletion in NRXN1 . © 2013 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/97220/1/35780_ftp.pd