Delivering agile marketing projects: a view from practice

Successful marketing projects are vital to most organisations to ensure their survival. The paper advocates an 'agile approach' in creating effective marketing initiatives. It underscores the necessity of clearly defined objectives and internal efficiency, addressing power issues for optimal resource allocation. Brand definition, understanding the customer base through profiling, and implementing a differentiated, segmented approach are crucial aspects. The paper recommends data gathering for analysis and leveraging technology to support these projects, all encapsulated within the 'agile approach.' The research methodology involved a survey of literature, complemented by a semi-structured group interview with experienced UK-based marketing professionals. Inductive analysis was applied to the gathered data, extracting principal themes. The outcome of this research proposes a framework for delivering 'Agile marketing projects' based on a project management 'learning' model. This structured approach contributes valuable insights for organizations seeking success in their marketing endeavors

Analysis of genetic variability in Turner syndrome linked to long-term clinical features

Background: Women with Turner syndrome (TS) (45,X and related karyotypes) have an increased prevalence of conditions such as diabetes mellitus, obesity, hypothyroidism, autoimmunity, hypertension, and congenital cardiovascular anomalies (CCA). Whilst the risk of developing these co-morbidities may be partly related to haploinsufficiency of key genes on the X chromosome, other mechanisms may be involved. Improving our understanding of underlying processes is important to develop personalized approaches to management. // Objective: We investigated whether: 1) global genetic variability differs in women with TS, which might contribute to co-morbidities; 2) common variants in X genes - on the background of haploinsufficiency - are associated with phenotype (a “two-hit” hypothesis); 3) the previously reported association of autosomal TIMP3 variants with CCA can be replicated. // Methods: Whole exome sequencing was undertaken in leukocyte DNA from 134 adult women with TS and compared to 46,XX controls (n=23), 46,XX women with primary ovarian insufficiency (n=101), and 46,XY controls (n=11). 1) Variability in autosomal and X chromosome genes was analyzed for all individuals; 2) the relation between common X chromosome variants and the long-term phenotypes listed above was investigated in a subgroup of women with monosomy X; 3) TIMP3 variance was investigated in relation to CCA. // Results: Standard filtering identified 6,457,085 autosomal variants and 126,335 X chromosome variants for the entire cohort, whereas a somatic variant pipeline identified 16,223 autosomal and 477 X chromosome changes. 1) Overall exome variability of autosomal genes was similar in women with TS and control/comparison groups, whereas X chromosome variants were proportionate to the complement of X chromosome material; 2) when adjusted for multiple comparisons, no X chromosome gene/variants were strongly enriched in monosomy X women with key phenotypes compared to monosomy X women without these conditions, although several variants of interest emerged; 3) an association between TIMP3 22:32857305:C-T and CCA was found (CCA 13.6%; non-CCA 3.4%, p<0.02). // Conclusions: Women with TS do not have an excess of genetic variability in exome analysis. No obvious X-chromosome variants driving phenotype were found, but several possible genes/variants of interest emerged. A reported association between autosomal TIMP3 variance and congenital cardiac anomalies was replicated

Multi-scale habitat selection throughout the annual cycle of a long-distance avian migrant

Long-distance migrants are constrained by widely separated hospitable habitats in geographically isolated locations, making them vulnerable to environmental change, both through natural and anthropogenic causes. Knowledge about their resource selection decisions is imperative to understand the drivers of their declines. The distinct periods within an annual cycle, when individuals experience different environmental circumstances, are inextricably linked through carry-over effects which can have important consequences for the individual, and consequently the population. In this study, we employ precise archival GPS-tracking data of European Nightjars (Caprimulgus europaeus) and high-resolution global land cover data to examine habitat selection during the sedentary wintering and breeding periods, as well as during autumn and spring migration, using a correlational approach. We demonstrate how nightjars use general habitat characteristics, such as landscape diversity, for high-order habitat selection, while resource selection at a finer spatial scale is reliant on fine-scale variables related to a habitat’s suitability, such as surface area of grassland and shrubland. We show that nightjars favour spatially diverse landscapes, which allows them to minimize time spent searching for optimal habitats. The considerable variation in the drivers of habitat selection between and within seasons shows how anthropogenic land-use change can have an array of different impacts on migrants by influencing large- and fine-scale habitat selection. This study shows the advantages of an individual based GPS-tracking approach, combined with high spatial resolution remote sensing data, and highlights the need for full annual-cycle research on scale dependent habitat selection of long-distance avian migrants

Australia\u27s health 1994 : the fourth biennial report of the Australian Institute of Health and Welfare

Australia\u27s Health is the most comprehensive and authoritative source of national information on health in Australia. Australia\u27s Health is published mid-year in even-numbered years and provides national statistics and related information that form a record of health status, service provision and expenditure in Australia

Cell-surface signatures of immune dysfunction risk-stratify critically ill patients: INFECT study.

PURPOSE: Cellular immune dysfunctions, which are common in intensive care patients, predict a number of significant complications. In order to effectively target treatments, clinically applicable measures need to be developed to detect dysfunction. The objective was to confirm the ability of cellular markers associated with immune dysfunction to stratify risk of secondary infection in critically ill patients. METHODS: Multi-centre, prospective observational cohort study of critically ill patients in four UK intensive care units. Serial blood samples were taken, and three cell surface markers associated with immune cell dysfunction [neutrophil CD88, monocyte human leucocyte antigen-DR (HLA-DR) and percentage of regulatory T cells (Tregs)] were assayed on-site using standardized flow cytometric measures. Patients were followed up for the development of secondary infections. RESULTS: A total of 148 patients were recruited, with data available from 138. Reduced neutrophil CD88, reduced monocyte HLA-DR and elevated proportions of Tregs were all associated with subsequent development of infection with odds ratios (95% CI) of 2.18 (1.00-4.74), 3.44 (1.58-7.47) and 2.41 (1.14-5.11), respectively. Burden of immune dysfunction predicted a progressive increase in risk of infection, from 14% for patients with no dysfunction to 59% for patients with dysfunction of all three markers. The tests failed to risk stratify patients shortly after ICU admission but were effective between days 3 and 9. CONCLUSIONS: This study confirms our previous findings that three cell surface markers can predict risk of subsequent secondary infection, demonstrates the feasibility of standardized multisite flow cytometry and presents a tool which can be used to target future immunomodulatory therapies. TRIAL REGISTRATION: The study was registered with clinicaltrials.gov (NCT02186522).The study was funded by Innovate UK (Sepsis 2: 101193), BD Biosciences and the National Institute for Academic Anaesthesia. Dr Conway Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z). Dr Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16- 011)

Pathogenic variants in the human m(6)A reader YTHDC2 are associated with primary ovarian insufficiency

Primary ovarian insufficiency (POI) affects 1% of women and carries significant medical and psychosocial sequelae. Approximately 10% of POI has a defined genetic cause, with most implicated genes relating to biological processes involved in early fetal ovary development and function. Recently, Ythdc2, an RNA helicase and N6-methyladenosine reader, has emerged as a regulator of meiosis in mice. Here, we describe homozygous pathogenic variants in YTHDC2 in 3 women with early-onset POI from 2 families: C. 2567C>G, p.P856R in the helicase-associated (HA2) domain and c.1129G>T, p.E377*. We demonstrated that YTHDC2 is expressed in the developing human fetal ovary and is upregulated in meiotic germ cells, together with related meiosisassociated factors. The p.P856R variant resulted in a less flexible protein that likely disrupted downstream conformational kinetics of the HA2 domain, whereas the p.E377*variant truncated the helicase core. Taken together, our results reveal that YTHDC2 is a key regulator of meiosis in humans and pathogenic variants within this gene are associated with POI

Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study.

PURPOSE: Reliable biomarkers for predicting subsequent sepsis among patients with suspected acute infection are lacking. In patients presenting to emergency departments (EDs) with suspected acute infection, we aimed to evaluate the reliability and discriminant ability of 47 leukocyte biomarkers as predictors of sepsis (Sequential Organ Failure Assessment score ≥ 2 at 24 h and/or 72 h following ED presentation). METHODS: In a multi-centre cohort study in four EDs and intensive care units (ICUs), we standardised flow-cytometric leukocyte biomarker measurement and compared patients with suspected acute infection (cohort-1) with two comparator cohorts: ICU patients with established sepsis (cohort-2), and ED patients without infection or systemic inflammation but requiring hospitalization (cohort-3). RESULTS: Between January 2014 and February 2016, we recruited 272, 59 and 75 patients to cohorts 1, 2, and 3, respectively. Of 47 leukocyte biomarkers, 14 were non-reliable, and 17 did not discriminate between the three cohorts. Discriminant analyses for predicting sepsis within cohort-1 were undertaken for eight neutrophil (cluster of differentiation antigens (CD) CD15; CD24; CD35; CD64; CD312; CD11b; CD274; CD279), seven monocyte (CD35; CD64; CD312; CD11b; HLA-DR; CD274; CD279) and a CD8 T-lymphocyte biomarker (CD279). Individually, only higher neutrophil CD279 [OR 1.78 (95% CI 1.23-2.57); P = 0.002], higher monocyte CD279 [1.32 (1.03-1.70); P = 0.03], and lower monocyte HLA-DR [0.73 (0.55-0.97); P = 0.03] expression were associated with subsequent sepsis. With logistic regression the optimum biomarker combination was increased neutrophil CD24 and neutrophil CD279, and reduced monocyte HLA-DR expression, but no combination had clinically relevant predictive validity. CONCLUSIONS: From a large panel of leukocyte biomarkers, immunosuppression biomarkers were associated with subsequent sepsis in ED patients with suspected acute infection. CLINICAL TRIAL REGISTRATION: NCT02188992.The study was funded by Innovate UK (Sepsis 2: 101193). Dr Shankar-Hari is supported by the National Institute for Health Research Clinician Scientist Award (CS-2016-16-011). Dr Conway Morris is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z)

Sustainable Diets: another hurdle or a better food future?,

The notion of sustainable diets has emerged forcibly onto the food policy agenda in recent years, but has also met resistance. The article reviews the case for sustainable diets. It counterbalances the current dominant policy emphasis on raising food output as the best route to a sustainable food future. The article suggests that a process of democratic experimentation is underway. Some official guidelines have emerged alongside a mix of civil society and academic formulations. More coherence of data, principles and purpose is needed at the global and regional policy-making levels for these to become effective in the common task of reducing the food system’s negative impact on health, environment and economies

Ten-year mortality, disease progression, and treatment-related side effects in men with localised prostate cancer from the ProtecT randomised controlled trial according to treatment received

Background The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy. Objective To report outcomes according to treatment received in men in randomised and treatment choice cohorts. Design, setting, and participants This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy. Intervention Two cohorts included 1643 men who agreed to be randomised and 997 who declined randomisation and chose treatment. Outcome measurements and statistical analysis Analysis was carried out to assess mortality, metastasis and progression and health-related quality of life impacts on urinary, bowel, and sexual function using patient-reported outcome measures. Analysis was based on comparisons between groups defined by treatment received for both randomised and treatment choice cohorts in turn, with pooled estimates of intervention effect obtained using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores. Results and limitations According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p = 0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p = 0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6 mo) and urinary incontinence (55% at 6 mo) after surgery, and of sexual dysfunction (88% at 6 mo) and bowel dysfunction (5% at 6 mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and changes in the protocol for AM during the lengthy follow-up required in trials of screen-detected PCa. Conclusions Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group. Patient summary More than 95 out of every 100 men with low or intermediate risk localised prostate cancer do not die of prostate cancer within 10 yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are better after active monitoring, but the risks of spreading of prostate cancer are more common