HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

A scoping review: Strategic workforce planning in health and social care

YesAim This aim of this scoping review was to undertake a detailed review of the pertinent literature examining strategic workforce planning in the health and social care sectors. The scoping review was tasked to address the following three questions: 1. How is strategic health and social care workforce planning currently undertaken? 2. What models, methods, and tools are available for supporting strategic health and social care workforce planning? 3. What are the most effective methods for strategic health and social care workforce planning? Methods The scoping review utilised the five-stage scoping review framework proposed by Arksey and O’Malley (2005). This includes identifying the research question; identifying relevant studies; study selection; charting the data and collating, summarizing, and reporting the results. The search included a range of databases and key search terms included “workforce” OR “human resource*” OR “personnel” OR “staff*”. Relevant documents were selected through initially screening titles and abstracts, followed by full text screening of potentially relevant documents. Results The search returned 6105 unique references. Based on title and abstract screening, 654 were identified as potentially relevant. Screening of full texts resulted in 115 items of literature being included in the synthesis. Both national and international literature covers strategic workforce planning, with all continents represented, but with a preponderance from high income nations. The emphasis in the literature is mainly on the healthcare workforce, with few items on social care. Medical and dental workforces are the predominate groups covered in the literature, although nursing and midwifery are also discussed. Other health and social care workers are less represented. A variety of categories of workforce planning methods are noted in the literature that range from determining the workforce using supply and demand, practitioner to population ratios, needs based approach, the utilisation of methods such as horizon scanning, modelling, and scenario planning, together with mathematical and statistical modelling. Several of the articles and websites include specific workforce planning models that are nationally and internationally recognised, e.g., the workload indicators of staffing needs (WISN), Star model and the Six Step Methodology. These models provide a series of steps to help with workforce planning and tend to take a more strategic view of the process. Some of the literature considers patient safety and quality in relation to safe staffing numbers and patient acuity. The health and social care policies reviewed include broad actions to address workforce planning, staff shortages or future service developments and advocate a mixture of developing new roles, different ways of working, flexibility, greater integrated working and enhanced used of digital technology. However, the policies generally do not include workforce models or guidance about how to achieve these measures. Overall, there is an absence in the literature of studies that evaluate what are the most effective methods for strategic health and social care planning. Recommendations The literature suggests the need for the implementation of a strategic approach to workforce planning, utilising a needs-based approach, including horizon scanning and scenarios. This could involve adoption of a recognised workforce planning model that incorporates the strategic elements required for workforce planning and a ‘one workforce’ approach across health and social care

Strategic workforce planning in health and social care - an international perspective: A scoping review

YesEffective strategic workforce planning for integrated and co-ordinated health and social care is essential if future services are to be resourced such that skill mix, clinical practice and productivity meet population health and social care needs in timely, safe and accessible ways globally. This review presents international literature to illustrate how strategic workforce planning in health and social care has been undertaken around the world with examples of planning frameworks, models and modelling approaches. The databases Business Source Premier, CINAHL, Embase, Health Management Information Consortium, Medline and Scopus were searched for full texts, from 2005 to 2022, detailing empirical research, models or methodologies to explain how strategic workforce planning (with at least one-year horizon) in health and/or social care has been undertaken, yielding ultimately 101 included references. The supply/demand of differentiated medical workforce was discussed in 25 references. Nursing and midwifery were characterised as undifferentiated labour, requiring urgent growth to meet demand. Unregistered workers were poorly represented as was the social care workforce. One reference considered planning for heath and social care workers. Workforce modelling was illustrated in 66 references with predilection for quantifiable projections. Increasingly needs-based approaches were called for to better consider demography and epidemiological impacts. This review’s findings advocate for whole-system needs-based approaches that consider the ecology of co-produced health and social care workforce.Claire Sutton and Julie Prowse are seconded (from February 2022 to March 2023) to the Workforce Observatory, the University of Bradford, West Yorkshire. Their research posts at the Workforce Observatory are funded by Health Education England

Alternative HER/PTEN/Akt Pathway Activation in HPV Positive and Negative Penile Carcinomas

Copyright: 2011 Stankiewicz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its impact on Akt activation using immunohistochemistry and fluorescent in situ hybridisation (FISH). Methodology/Principal Findings: 148 PSCCs were microarrayed and immunostained for phosphorylated EGFR (pEGFR), HER2, HER3, HER4, phosphorylated Akt (pAkt), Akt1 and PTEN proteins. EGFR and PTEN gene status were also evaluated using FISH. HPV presence was assessed by PCR. pEGFR expression was detected significantly less frequently in HPV-positive than HPV-negative tumours (p = 0.0143). Conversely, HER3 expression was significantly more common in HPV-positive cases (p = 0.0128). HER4, pAkt, Akt and PTEN protein expression were not related to HPV. HER3 (p = 0.0054) and HER4 (p = 0.0002) receptors significantly correlated with cytoplasmic Akt1 immunostaining. All three proteins positively correlated with tumour grade (HER3, p = 0.0029; HER4, p = 0.0118; Akt1, p = 0.0001). pEGFR expression correlated with pAkt but not with tumour grade or stage. There was no EGFR gene amplification. HER2 was not detected. PTEN protein expression was reduced or absent in 62% of tumours but PTEN gene copy loss was present only in 4% of PSCCs. Conclusions/Significance: EGFR, HER3 and HER4 but not HER2 are associated with penile carcinogenesis. HPV-negative tumours tend to express significantly more pEGFR than HPV-positive cancers and this expression correlates with pAkt protein, indicating EGFR as an upstream regulator of Akt signalling in PSCC. Conversely, HER3 expression is significantly more common in HPV-positive cases and positively correlates with cytoplasmic Akt1 expression. HER4 and PTEN protein expression are not related to HPV infection. Our results suggest that PSCC patients could benefit from therapies developed to target HER receptors.Peer reviewedFinal Published versio

Macrophage migration inhibitory factor (MIF) is essential for type 2 effector cell immunity to an intestinal helminth parasite

Immunity to intestinal helminths is known to require both innate and adaptive components of the immune system activated along the Type 2 IL-4R/STAT6-dependent pathway. We have found that macrophage migration inhibitory factor (MIF) is essential for the development of effective immunity to the intestinal helminth Heligmosomoides polygyrus, even following vaccination which induces sterile immunity in wild-type mice. A chemical inhibitor of MIF, 4-IPP, was similarly found to compromise anti-parasite immunity. Cellular analyses found that the adaptive arm of the immune response, including IgG1 antibody responses and Th2-derived cytokines, was intact and that Foxp3+ T regulatory cell responses were unaltered in the absence of MIF. However, MIF was found to be an essential cytokine for innate cells, with ablated eosinophilia and ILC2 responses, and delayed recruitment and activation of macrophages to the M2 phenotype (expressing Arginase 1, Chil3, and RELM-α) upon infection of MIF-deficient mice; a macrophage deficit was also seen in wild-type BALB/c mice exposed to 4-IPP. Gene expression analysis of intestinal and lymph node tissues from MIF-deficient and -sufficient infected mice indicated significantly reduced levels of Arl2bp, encoding a factor involved in nuclear localization of STAT3. We further found that STAT3-deficient macrophages expressed less Arginase-1, and that mice lacking STAT3 in the myeloid compartment (LysMCrexSTAT3fl/fl) were unable to reject a secondary infection with H. polygyrus. We thus conclude that in the context of a Type 2 infection, MIF plays a critical role in polarizing macrophages into the protective alternatively-activated phenotype, and that STAT3 signaling may make a previously unrecognized contribution to immunity to helminths

Canadian infants' nutrient intakes from complementary foods during the first year of life

<p>Abstract</p> <p>Background</p> <p>Complementary feeding is currently recommended after six months of age, when the nutrients in breast milk alone are no longer adequate to support growth. Few studies have examined macro- and micro-nutrient intakes from complementary foods (CF) only. Our purpose was to assess the sources and nutritional contribution of CF over the first year of life.</p> <p>Methods</p> <p>In July 2003, a cross-sectional survey was conducted on a nationally representative sample of mothers with infants aged three to 12 months. The survey was administered evenly across all regions of the country and included a four-day dietary record to assess infants' CF intakes in household (tablespoon) measures (breast milk and formula intakes excluded). Records from 2,663 infants were analyzed for nutrient and CF food intake according to 12 categories. Mean daily intakes for infants at each month of age from CF were pooled and compared to the Dietary Reference Intakes for the respective age range.</p> <p>Results</p> <p>At three months of age, 83% of infants were already consuming infant cereals. Fruits and vegetables were among the most common foods consumed by infants at all ages, while meats were least common at all ages except 12 months. Macro- and micro-nutrient intakes from CF generally increased with age. All mean nutrient intakes, except vitamin D and iron, met CF recommendations at seven to 12 months.</p> <p>Conclusions</p> <p>Complementary foods were introduced earlier than recommended. Although mean nutrient intakes from CF at six to 12 months appear to be adequate among Canadian infants, further attention to iron and vitamin D intakes and sources may be warranted.</p

Making machine intelligence less scary for criminal analysts: reflections on designing a visual comparative case analysis tool

A fundamental task in Criminal Intelligence Analysis is to analyze the similarity of crime cases, called CCA, to identify common crime patterns and to reason about unsolved crimes. Typically, the data is complex and high dimensional and the use of complex analytical processes would be appropriate. State-of-the-art CCA tools lack flexibility in interactive data exploration and fall short of computational transparency in terms of revealing alternative methods and results. In this paper, we report on the design of the Concept Explorer, a flexible, transparent and interactive CCA system. During this design process, we observed that most criminal analysts are not able to understand the underlying complex technical processes, which decrease the users' trust in the results and hence a reluctance to use the tool}. Our CCA solution implements a computational pipeline together with a visual platform that allows the analysts to interact with each stage of the analysis process and to validate the result. The proposed Visual Analytics workflow iteratively supports the interpretation of the results of clustering with the respective feature relations, the development of alternative models, as well as cluster verification. The visualizations offer an understandable and usable way for the analyst to provide feedback to the system and to observe the impact of their interactions. Expert feedback confirmed that our user-centred design decisions made this computational complexity less scary to criminal analysts