Women living with HIV – carrying the burden of the pandemic.

Source: Sophia Forum – We are still here – accessed 25-10-21

All groups affected by HIV should have access to appropriate care and the opportunity to, for instance, enter clinical trials and access innovative treatments. A recent editorial noted the mismatch between those PLWH that were recruited to clinical trials (overrepresentation of young white males) and those seen in the general population (a more heterogeneric demography). Women have been severely underrepresented in many areas of HIV treatment and care including inclusion in research. This appears to be an ongoing issue across the HIV landscape with alternative approaches required to allow both access and opportunity in advancing care and its underpinning research. This is essential as in the UK a third of people living with HIV are women and globally the figure stands at fifty percent and it is incumbent on everyone that the right interventions are utilised in this as well as any other community. This is particularly important where intersectional issues make marginalisation and stigma even more challenging.  The near-invisibility of WLWH is not a recent phenomenon but one that has existed from the early 80s when HIV came to the fore and the public’s attention.  This is one legacy that the community needs to overcome and as Jacqui Stevenson says:

No more excuses: Making HIV research work for women. (Sophia Forum)

Other marginalised groups such as those from BAME backgrounds, whilst being disproportionately affected, were also largely excluded from trials and medical care more generally.

As ART has produced improved outcomes in terms of life expectancy, the demographics of people living with HIV has changed radically. A significant number of PLWH including women have a life expectancy similar to that found in the general population.  However, there are disparities between groups (see, for instance, Solomon et al 2020) and a general reduction in quality of life for PLWH due to the onset of a range of geriatric syndromes a decade or more earlier with ongoing discrimination. This has been emphasised recently by ongoing research and advocacy by Jacqui Stevenson who has studied WLWH growing older. The outcomes of the research provide eight asks to improve the lives of WLWH.

Advice for women and HIV including using PrEP can be found at:

UKRI Reviews of Doctoral Training – The Good and Some Cause for Concern

The UKRI, the overarching government body that manages publicly funded research and innovation in the UK, has just published two reports on doctoral training one in STEM (the EPSRC report) and one by the equivalent in social sciences (the ESRC report). Both reports recognise the value of doctoral training with an emphasis on employers rather than the wider community. The reports highlight the need for future action in this area:

Alongside council-specific actions, the two reviews are also an important contribution to the evidence base for a new deal for postgraduate research, which will address:

  • funding and stipend levels
  • routes in, through and out of doctoral training
  • rights and conditions
  • diversification of models and access.

UKRI – https://www.ukri.org/news/epsrc-and-esrc-doctoral-reviews-published/ accessed 10-10-2021

The EPSRC has released its review of doctoral training in the STEM arena within the UK. There is a wealth of information on the background to the report including outcomes from workshops with stakeholders and a review of the current literature. There is also the report itself and the recommendations therein.

List of recommendations  
Recommendation 1 To stimulate economic growth, EPSRC should increase the number of students it supports and the professional development that they receive. EPSRC-funded doctoral students go onto careers in innovation and research in manufacturing, information and communication technologies and other scientific and technical careers in industry and academia. To become a global science superpower, the number of people with these skills must grow and EPSRC must lead by increasing the number of students it supports. EPSRC should bid for an uplift of investment in EPS for doctoral education from the spending review and other opportunities.
Recommendation 2 EPSRC should better demonstrate the value of a doctorate, its outcomes, and the destination of doctoral graduates, so that this is understood by all key stakeholders.
Recommendation 3 EPSRC should continue to provide thought leadership in doctoral education to the EPS community by investing in the highest quality doctoral education provision which supports a diverse range of career paths.
Recommendation 4 EPSRC should provide a stable long-term baseline of investment to support a creative and innovative fundamental research community (such as the current algorithmic DTP investment), alongside a more dynamic framework to respond to and support emerging strategic priorities (for example by investing in more frequent CDT competitions and including studentship investments alongside research investments in top priority strategic areas).
Recommendation 5 To effectively support the UK’s increasing STEM capability, the system as a whole needs to grow. Recognising the high value placed on doctoral studentships by industry, EPSRC should engage with industry (both the current and new sectors) to encourage and enable increased industry funding and co-funding of doctoral students. These are effective ways of attracting industry investment into the R&D landscape.
Recommendation 6 EPSRC should showcase the ways small and medium enterprises can and do engage with doctoral students, to widen participation and enable overall growth in the system.
Recommendation 7 EPSRC should work with UKRI on doctoral student issues covered by the Government’s People and Culture Strategy expected to be published in summer 2021, ensuring that issues facing the EPS community are addressed. In particular, the New Deal for postgraduate research is expected to address areas such as the stipend level for doctoral students, the rights and conditions of doctoral studentships, financial sustainability of doctoral education investments, doctoral student recruitment policies, and the health and wellbeing of students.
Recommendation 8 The existing opportunity to employ graduates on UKRI grants does not replace our main route to doctoral education but could provide a valuable alternative career
Recommendation 9 EPSRC should work with the sector to provide greater recognition and visibility of the wider skills developed alongside research skills during a doctorate to ensure the employability of all doctoral graduates.
Recommendation 10 All EPSRC funded students should have access to opportunities outside of their research project (e.g., conferences, placements, public engagement), irrespective of the funding route. EPSRC should be explicit within each scheme that funding should be made available for opportunities outside of the research project.
Recommendation 11 EPSRC should prioritise funding excellent doctoral experiences and access to opportunities over student numbers, while ensuring value for money.
Recommendation 12 EPSRC should assist those who deliver the EPSRC doctoral investments in developing and sharing good practice.
Recommendation 13 It is essential that EPSRC continues to invest through a diverse range of flexible approaches so that we continue to support doctoral students’ varied needs, backgrounds and potential careers as well as the differing requirements of the research and innovation communities.
Recommendation 14 As EPSRC’s current mechanisms are well regarded, new initiatives should only be introduced where there is a compelling case for an alternative approach.
Recommendation 15 EPSRC should work with all stakeholders to ensure the current flexibilities relating to both collaboration and supporting students are well known and used.
Recommendation 16 Doctoral education should be available to people following a variety of career paths. EPSRC should work with stakeholders to continue to improve access, diversity of entry points to doctoral education and tailored support for individuals.
Recommendation 17 EPSRC should understand detailed EDI issues in each of our research areas or sectors and work with our community and representative bodies to address them. EPSRC will continue to work within UKRI on broader EDI initiatives.
Recommendation 18 EPSRC should explore how doctoral training investments can support the levelling up agenda.

Conspiracy theories as new pandemics arise… the role of the scientist!

Word Cloud from a set of Guardian posts on the origins of HIV

While reading the literature for a forthcoming grant submission on aspects of the HIV pandemic, I came across several articles both within and outside the mainstream media that relate to the development and spread of troubling assertions. These concern, for instance, the origin of HIV and an implied role of politicians in restricting or encouraging certain avenues of development to maintain industries’ pre-eminent economic position and profit-making. Sometimes these assertions develop into conspiracy theories which are explained, at a later date, in relatively simple terms, as is the case in recognising HIV sequences in the SARS-Cov-2 virus. Here, a bit more thought and critical evaluation would have prevented this avenue of thought, but instead it was posted on a pre-print server for all to see and then subsequently withdrawn, but not before the ‘engineered’ virus concept had taken hold in certain areas of the media.  The simple explanation was that a number of viruses have these sequences.

So what, as scientists, are we to do about preventing such misrepresentations in terms of engaging the public and our own self-management? Here are some thoughts:

  • Employ the skills that are central to our work as scientists, indeed as researchers more broadly, of checking, validating and providing critical insight to our work.  This is particularly important in the medical field generally, but in pandemics specifically, where there may be a heightened awareness of our own frailty and fear of new pathogens that arise from time to time.
  • Personally, I am concerned by the rise in the production of pre-prints from a niche activity to one that has now become mainstream. I suspect this is motivated by data-driven metrics (citations but also prestige) as well as the ‘first to print’, which may be important in exploiting base technologies. It can be argued, however, that this rapid dissemination of information is key, not only in developing collaborative research, especially in times of a pandemic, but also in allowing the quick development of frameworks and insights that may otherwise take months to generate if the peer-review process had to be adhered to. To protect both the research community and the wider public, servers hosting pre-prints have strengthened their assessment procedures once an article is posted. Nature Cancer provides a more nuanced overview of this issue as does the Lancet.
  • We should take it upon ourselves to assess the risks involved in how we report scientific findings, asking ourselves whether our published work can be misconstrued or misrepresented so as to allow a false discourse to emerge that can create a situation that does more harm than good.  I am not suggesting, in any form, that we should self-censor but there may be better ways of disseminating information to allow a more constructive debate.  A lack of transparency can also lead to a rise in misinformation, although we should endeavour to realise that the relationship between opaqueness, conspiracies and power, in the eyes of the public and other stakeholder groups, is a complex one and there are no easy fixes.
  • Following on from this we should aim to provide the public with timely information (see my second point) that adds to the debate, treats the individual or group with respect and takes out of the communication moralising (our prejudice) about their behaviour or activity. This is a multidisciplinary arena which works most effectively when it engages people from different disciplines and stakeholder groups to develop strategies relevant to the target cohort(s).
  • Words (and deeds) matter – choose your words carefully and have consideration for the cultural as well as scientific aspects of the cohorts’ living status.  Using certain words and phrases, however well meaning, can alienate, disenfranchise, further stigmatise and evoke distrust in the individuals or groups we are trying to help.  This applies across a range of illnesses and traumas, but particularly so for those in which there is significant stigma, such as mental health and HIV. In doing so, and where you can, try to make it a two-way dialogue and place the person we are trying to help at the centre of the research – co-create and co-produce – and ensure their contribution is valued.

Those outside science, medicine and research also have responsibilities, especially those that are in positions which require them to uphold given behaviour and adhere to certain protocols or codes of conduct. This is particularly important when using frameworks to build trust between stakeholders in the public at large and the wider concept of ‘truth’.

These are just a few thoughts and are not meant to be definitive answers. But I do hope to stimulate some debate.

Cartilage Tissue Engineering and Electrospinning

Cartilage-related diseases are a promising field to explore in tissue engineering and regenerative medicine. The cartilage hydrated structure is aneural, avascular, and non-lymphatic, which complicates natural regeneration [1,2]. The increase in life expectancy and obesity is directly correlated to osteoarthritis –the disease caused by the degradation of cartilage. The painful consequences also increase comorbidities and burden patients and healthcare providers with exorbitant costs [3,4].

Currently, surgical and non-surgical therapies are employed to address osteoarthritis. They are not permanent solutions [5–7]. Therefore, several groups are developing hydrogels [8,9], electrospun mats [10], and other biomaterials to mimic the natural properties of cartilage. These implants can increase patients’ quality of life, reducing pain, comorbidities, and other undesirable effects after their clinical trials and regulatory agency approval.

 

Chondrocyte proliferation on neutralized chitosan fiber mats. Image adapted from https://doi.org/10.1016/j.fhfh.2021.100018 under Creative Commons License

Yilmaz and Zeugolis discuss the promises, challenges, and future perspectives of electrospinning applied to cartilage tissue engineering [11]. They emphasize that although electrospinning literature is abundant in the Pubmed database, few studies explore electrospining’s potential applied to cartilage tissue engineering. The authors demonstrate with pre-clinical results that stem cell-seeded electrospun scaffolds combined with other techniques (3D printing and freeze-drying) can recover lubricating properties, mechanical resistance and restore cartilage tissue properties [11]. Although the reviewed studies consider small animals (rats, mice, and rabbits), they are promising to people suffering from the pain and harmful effects of osteoarthritis worldwide [11].

 

This article was written by André Plath as part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

André is researching Boundary Lubrication of Fibrous Scaffolds at ETH Zürich, Switzerland.

.

 

 

[1]        L.M. Billesberger, K.M. Fisher, Y.J. Qadri, R.L. Boortz-Marx, Procedural Treatments for Knee Osteoarthritis: A Review of Current Injectable Therapies, Pain Res. Manag. 2020 (2020) 1–11. https://doi.org/10.1155/2020/3873098.

[2]        E.D. Bonnevie, V.J. Baro, L. Wang, D.L. Burris, Fluid load support during localized indentation of cartilage with a spherical probe, J. Biomech. 45 (2012) 1036–1041. https://doi.org/10.1016/j.jbiomech.2011.12.019.

[3]        S. Glyn-Jones, A.J.R. Palmer, R. Agricola, A.J. Price, T.L. Vincent, H. Weinans, A.J. Carr, Osteoarthritis, in: Lancet, Lancet Publishing Group, 2015: pp. 376–387. https://doi.org/10.1016/S0140-6736(14)60802-3.

[4]        D.J. Hunter, L. March, M. Chew, Osteoarthritis in 2020 and beyond: a Lancet Commission, Lancet. 396 (2020) 1711–1712. https://doi.org/10.1016/S0140-6736(20)32230-3.

[5]        Y. Lee, J. Choi, N.S. Hwang, Regulation of lubricin for functional cartilage tissue regeneration: a review, Biomater. Res. 22 (2018) 9. https://doi.org/10.1186/s40824-018-0118-x.

[6]        G. Musumeci, C. Loreto, M.L. Carnazza, F. Coppolino, V. Cardile, R. Leonardi, Lubricin is expressed in chondrocytes derived from osteoarthritic cartilage encapsulated in poly(ethylene glycol) diacrylate scaffold, Eur. J. Histochem. 55 (2011) 31. https://doi.org/10.4081/ejh.2011.e31.

[7]        W. Kabir, C. Di Bella, I. Jo, D. Gould, P.F.M. Choong, Human Stem Cell Based Tissue Engineering for In Vivo Cartilage Repair: A Systematic Review, Tissue Eng. Part B Rev. 27 (2021). https://doi.org/10.1089/ten.teb.2020.0155.

[8]        Y. Gombert, R. Simič, F. Roncoroni, M. Dübner, T. Geue, N.D. Spencer, Structuring Hydrogel Surfaces for Tribology, Adv. Mater. Interfaces. 6 (2019) 1901320. https://doi.org/10.1002/admi.201901320.

[9]        M. Jurak, A.E. Wiącek, A. Ładniak, K. Przykaza, K. Szafran, What affects the biocompatibility of polymers?, Adv. Colloid Interface Sci. 294 (2021) 102451. https://doi.org/10.1016/j.cis.2021.102451.

[10]      J.K. Wise, A.L. Yarin, C.M. Megaridis, M. Cho, Chondrogenic Differentiation of Human Mesenchymal Stem Cells on Oriented Nanofibrous Scaffolds: Engineering the Superficial Zone of Articular Cartilage, Tissue Eng. Part A. 15 (2009) 913–921. https://doi.org/10.1089/ten.tea.2008.0109.

[11]      E.N. Yilmaz, D.I. Zeugolis, Electrospun Polymers in Cartilage Engineering—State of Play, Front. Bioeng. Biotechnol. 8 (2020). https://doi.org/10.3389/fbioe.2020.00077.

Validation and Verification

Collectively, verification and validation are a cornerstone of many areas of research, none more so that in engineering and the physical sciences. Yet many early stage researchers have yet to appreciate their definitions or fully understand the signficance of these activities.  William Morales’, blog provides a brief introduction to Device Design Verification and Validation – useful for those just beginning in their careers in the MedTech arena or indeed anyone who needs a quick refresher.  However, there is still of lot of discussion about the use of the terms particulary between fields as there maybe nuances or historical context that means the defintions deviate – for instance the article at ResearchGate by Ryan and Wheatcroft (2017).  Simple defintions may employ something along the lines of:

  • verification - am I building something right
  • validation - am I building the right something

Software engineering, an increasingly important aspect of medical devices, especially through the rise of in situ/in vivo monitoring, has it owns definitions. Sargent defines the processes by which a researcher can V&V computational simulations whilst Viceconti et al (2021) discuss V&V for in silico trials.

Interesting paper that investigates corrosion and tribocorrosion behavior of binary and ternary carbide coatings for load-bearing implants

An exciting paper discussing the feasibility of binary and ternary carbide coatings for load-bearing implants with improved biocompatibility was published by Pana and co-workers in 2020. The peer-reviewed article was published in the Coatings journal and it is titled “In vitro corrosion and tribocorrosion performance of biocompatible carbide coatings”.

This work assessed elemental and phase composition, tribo-mechanical properties, corrosion and tribocorrosion of coatings deposited by cathodic arc evaporation on polished 316L SS discs (Ra = 50 ± 2 nm). TiNbC coating outperformed the other synthesized coatings in terms of initial surface roughness and corrosion resistance (shown by the lowest change in Ra before and after corrosion tests). Even though ZrC and TiNbC displayed similar polished wear tracks, the latter exhibited the lowest friction coefficient and wear rate on the tribocorrosion tests.

These results delivery an important advancement towards the development of coatings more biocompatible, presenting higher corrosion resistance along with improved tribocorrosion performance. The graphical abstract shown below showcases some of the results of this worth reading paper.

 

CC License – 4.0 International (CC BY 4.0) Pana, I.; Vladescu, A.; Constantin, L.R.; Sandu, I.G.; Dinu, M.; Cotrut, C.M. In Vitro Corrosion and Tribocorrosion Performance of Biocompatible Carbide Coatings. Coatings 2020, 10, 654. https://doi.org/10.3390/coatings10070654

 

This post was written by Pedro Luiz Lima dos Santos as part of an ongoing series of scientific communications written and curated by BioTrib’s Early Stage Researchers.

Pedro is researching the Functional Biotribology of the Surface Engineering of 3D Printed Components at the University of Leeds, UK.

Excellent paper from the Nu-Spine ETN – Congratulations to Seung and co-authors!

Seung Hun Lee and colleagues at ETH Zurich have recently published a peer reviewed paper “Comprehensive in vitro Comparison of Cellular and Osteogenic Response to Alternative Biomaterials for Spinal Implants” in Materials Science and Engineering: C. The article explored the effects of silicon nitride (SN) in terms of cell proliferation, mineralization and osteogenesis, all of which were deemed positive with respect to the effects of other materials including Ti and PEEK. A similar result to that of SiN was found for zirconia toughened alumina. Further, the paper demonstrates the potential of surface texturing in enhancing the osteogenic capacity of this material. The graphical abstract for the paper can be found below.

CC License – NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0).
Seunghun S. Lee, Stephanie Huber, Stephen J. Ferguson,
Comprehensive in vitro comparison of cellular and osteogenic response to alternative biomaterials for spinal implants,
Materials Science and Engineering: C, Volume 127, 2021, 112251, ISSN 0928-4931, https://doi.org/10.1016/j.msec.2021.112251.

Surface Modifications of Breast Implants affect Immune Response.

Further evidence of the important effect of engineered surfaces on immune response, this time in breast implants. Such research demonstrates the importance of modifying the surface texture in a manner that reduces the foreign body response. These and other examples pave the way for the development of new technologies for enhancing a favourable response to the implant and reduce complications including, potential, arising from infection and surface contraction.

The authors of the original paper have already provided a classification system for functional biocompatibility with regard to surface roughness (see figure below).


Figure reproduced from: Barr et al, Journal of the Mechanical Behavior of Biomedical Materials, Volume 75, November 2017, Pages 75-81.  Attribution 4.0 International (CC BY 4.0)

10,000 and counting – Congratulations to the ERC for reaching this impressive milestone!

The European Research Council has just awarded its 10,000th grant!  The award was an Consolidator Grant provided to Professor Inga Berre of the University of Bergen – congratulations! Not sure it is a milestone under the definition provided by the online manual for Horizon Europe, but BioTrib is not going to allow this to stop celebrating another EU Horizon success – champers out folks! To celebrate this fantastic achievement the ERC had a celebration attended by Senior EU dignitaries as well previous award winners outlining the support and subsequent impact such an award had on their careers and the wider community.

 

 

Research – Inspiring paper from the Leeds-Imperial Group on the Fabrication of Cartilage-Inspired Hydrogel Entangled Polymer–Elastomer Structures.

Significant paper developing and modelling hydrogels with a goal of more closely representing those of cartilage. The material shows a similar equilibrium compressive modulus to that observed in cartilage and allows for both rehydration and poroelastic lubrication mechanisms. BioTrib looks forward to seeing further work from this partnership of leading tribological and modelling groups.

Abstract Image

Figure – Reprinted with permission from: Fabrication of Cartilage-Inspired Hydrogel/Entangled Polymer–Elastomer Structures Possessing Poro-Elastic Properties, Siavash Soltanahmadi, Nicholas Raske, Gregory N. de Boer, et al.  ACS Applied Polymer Materials, Copyright 2021 American Chemical Society

 

Training – What skills does a PhD student need for a successful career outside academia?

Melina Papalampropoulou-Tsiridou has recently written an interesting blog on the PLOS ECR community pages which poses the following question:

PhD training in the 21st century: is there something missing?

This is a difficult question with the myriad of skills required in differing jobs across the STEM sector, from a science policy adviser to a postdoctoral researcher in a laboratory at a prestigious global University.  Indeed some of the skills required of a PhD student in industry may be become less important than they were in actually doing the PhD, whilst others will come to the fore once in paid employment post PhD.  An example, may be the focus on the idea of being an independent researcher, a student pursuing their own research goals, sometimes linked to other projects as in ETNs, sometimes not.  However, in industry, or even in EU funded large scale projects such as LifeLongJoints, the research is often completed in teams with groups of people explicitly working towards a common goal.  In it is not to say that PhDs are not highly prized, they are! Employers seek researchers with skills in critical analysis, a greater degree of objectivity and adept at generating new ideas. It is to be remembered that most PhDs will end up outside the academic sector.  In a recent BioTrib meeting with industry on supervisory training it was suggested that PhD candidates lack Project Management and other organisational skills when entering industry, but that the core creativity was highly valued. Melina provides similar examples around Networking and Management skills which appears to reflect a wider observation.  In BioTrib the Early Stage Researchers will undertake some Research Management training including Project Management, Ethics and aspects of Regulation. However, more can be done to make this more effective and embed this within European Research (Training) Programmes without impacting on the valuable core research that these ESRs do whilst undertaking a PhD.

If you want to outline what skills you think are missing in a PhD programme, please contact us here at BioTrib.

Armageddon… not quite but why don’t they stick scales on their photos!

Exciting news reported in the local papers in Gloucestershire as well as news nationally in the UK this week, as small meteorite hit the UK. First signs were a bright, extended meteor track shot on various door bell and security cameras, with a subsequent find by a bemused family on their driveway.  The family then alerted the experts (don’t tell Gove) who now reliably tell us it contains material from the beginning of the solar system.  Indeed one could argue that the material was probably from the Big Bang in one form or another, but that discussion is for another day.  But BBC and other media providers, please put a scale bar on your pics when there is no natural reference.  The meteorite itself could be any size and the picture of the drive could easily be of a coating on a metals surface of the order of a few microns or less or a stony desert!  Admittedly, if the latter were true the resulting impact would bring out more than a few avid meteorite hunters.

May this be a lesson for budding coating engineers – you don’t want your rather novel coating that is about to revolutionise joint replacement to be mistaken for a meteorite impact!

Health – COVID fightback: the critical role of HIV experts

An article in the Guardian highlights the critical skills needed to identify, treat and limit the impact of new diseases.  It is important these and other skills are retained as the global community moves forward in what may become a continuous battle for health security. The broader inputs from behavioural scientists and other stakeholders/participants in the social science field are equally important in our fight against current and emerging disease states as interventions depend on the public perception of risk and how this plays out in the community. This crucial piece of the jigsaw became apparent in the early stages of the HIV pandemic in the 80s and 90s.