Martin Braddock

AstraZeneca | AZ · Global Medicines Development

We invite you to submit proposals for chapters to the collective book titled “The Human Factor in a Hypothetic Encounter with Extra-terrestrials”. This is another volume in the “human factor” series devoted to the analysis of selected aspects of space missions. This time, we would like to take a multi-faceted look at the “human factor” in the conte...

The third in a series of articles reviewing progress, challenges and opportunities for the colonisation of Mars

Synthetic biology is a new and promising way of managing challenges which may be faced by astronauts during human space missions. Due to specific constraints, which include long term travel and future settlement where in-situ resources are limited, synthetic biology provides a rational solution. In this paper, we start from an evaluation of ethics...

Synthetic biology is a new and promising way of managing challenges which may be faced by astronauts during human space missions. Due to specific constraints, which include long term travel and future settlement where in-situ resources are limited, synthetic biology provides a rational solution. In this paper, we start from an evaluation of ethics...

Protection against the effects of space radiation poses great technical and medical challenges for future human missions and is of interparliamentary concern requiring alignment of multiple scientific, clinical, and ethical parameters. In our article, we highlight the inadequacy of current countermeasures, which may justify the use of human enhance...

Recent technical successes of the unmanned Mars 2020, Tianwen-1 and Hope Mars missions have further increased our hunger for space exploration and the possible colonisation of Mars is now firmly on the mid-term horizon. Furthermore, renewed commitment to settle on the Moon is anticipated within the next three years, led by NASA’s Artemis programme...

The development and deployment of robotics to assist humans working in, or at distance from extreme environments, such as the nuclear industry, high and low temperature environments, in offshore maintenance, the mega-construction industry and deep mining has rapidly progressed and may now be considered standard practice in many projects. In all ins...

Our understanding of the Moon has vastly increased since the 17th century when Dr John Wilkins first proposed the idea of colonising it. Today, with the development of additive manufacturing (AM), widely known as 3D printing, the concept of cost-effective lunar colonisation could soon become a reality. Here the authors consider what needs to be ach...

We sought to understand via crowd-sourcing from members of the Irish Astronomy community incidences, challenges for current a future management of wounds and injuries for astronauts and colonists in off-world environments. We have applied work domain analyses to the data which has been submitted for publication.

Discusses at a science popular level the role extremophiles may have played in panspermia and their utility in biotechnology on Earth

Lunar settlements will include industrial agriculture, so an artificial agricultural environment will be part of the landscape and work space for early settlements. Provision of capacity and development of new capabilities will pose both opportunities and risks for engineers, scientists and project managers. Lunar regolith is the layer of particles...

Lunar dust will arise as an issue for remediation in the earliest lunar settlements. The natural environment will pose risks that are becoming an important focus for research. Since Apollo 12 astronaut Alan Bean became accidentally exposed to lunar regolith in 1970, the toxic effects of Moon dust (<20 µm particle size diameter) and simulants have b...

Second of a series of articles reviewing progress, challenges and opportunities for colonisation of Mars

The physiological ramifications of living and working in microgravity and at elevated exposure levels to space radiation have been well documented. Exercise regimes and therapeutic intervention strategies have been devised and implemented to reduce soft and hard tissue atrophy during spaceflight. Nevertheless, effective countermeasures for both phy...

Future human space missions to Mars and beyond may be realized for different research, economic, political or survival reasons. Since space remains a hazardous environment for humans, space exploration and exploitation requires the development and deployment of effective countermeasures. In this paper, we discuss prospects for human enhancement by...

Rapid advances in biology, electronics, computer and data science have turned invention into products, changing the lives and lifestyles of millions of people around the world. This mini-review will describe some remarkable progress made over the last 10 years which serves both healthy individuals and patients alike. With a forward looking lens tow...

The recent success of the Mars 2020 project and the high quality images relayed back to Earth have provided further impetus and expectations for human missions to Mars. To support space agency and private enterprise plans to establish a sustainable colony on Mars in the 2030s, synthetic biology may play a vital role to enable astronaut self-suffici...

Challenges and opportunities for maximising lunar and Martian regolith are summarised at a popular science level

Presents at a science popular level how the space environment may assist drug discovery and development and help human health overall

The concept of black holes or completely collapsed gravitational objects as they were originally called has fascinated the scientific community and writers of science fiction for centuries. The mathematical proof of the existence of black holes came from the collation of multiple lines of evidence, some of which were highly debated and was derived...

Over recent years, challenges associated with planning the human exploration of deep-space in the near future have received increasing attention. The issues which should be considered are not solely confined to medical and technological, but also include political, social and ethical issues. Human space settlement may be regarded as the next step o...

First of a series of articles reviewing progress, challenges and opportunities for colonisation of Mars

Human beings are poorly adapted to live and work in space for long periods of time. This situation poses as yet insurmountable challenges for deep space travel and the colonisation of other worlds including those in our solar systems such as the Moon or Mars. Research road maps have been built by multi-disciplinary teams working internationally to...

As we look beyond our terrestrial boundary to a multi-planetary future for humankind, it becomes paramount to anticipate the challenges of various human factors on the most likely scenario for this future: permanent human settlement of Mars. Even if technical hurdles are circumvented to provide adequate resources for basic physiological and psychol...

The unique nature of microgravity encountered in space provides both an opportunity and challenge for drug discovery and development that cannot be fully replicated on Earth. Scientific studies have been conducted across most phases of the drug discovery value chain and include the generation of superior protein crystals, identification, and valida...

While humans have made enormous progress in the exploration and exploitation of Earth, exploration of outer space remains beyond current human capabilities. The principal challenges lie in current space technology and engineering which includes the protection of astronauts from the hazards of working and living in the space environment. These chall...

The human desire for exploration, together with an increasingly demanding potential need for establishing a human colony away from Earth has stimulated the concept and early planning for Mars colonisation. Successful delivery of such a challenging and expensive technological feat requires a highly informed and supportive general society. Although t...

Living and working in space presents many challenges for maintenance of optimal human physiology and psychology. The physical effects of microgravity and increased radiation exposure together with the psychological effects of isolation on human beings pose problems which are under intense investigation by global space agencies, corporate and academ...

Manned spaceflight is ergonomically constrained by living and working in a confined space in microgravity where astronauts on both short and long duration missions are exposed to daily radiation levels well above those received on Earth. Living in microgravity, especially on long duration missions aboard the International Space Station has deleteri...

Not mutually exclusive Objectives: review the three principle ergonomic constraints for astronauts undergoing space travel, describe how environmental adaptation may relieve these constraints and illustrate some opportunities for future space exploration based on either human crew or an e-crew of human avatars which utilise developing concepts in a...

Summary of poster presentation in the Ergonomist Apr/May edition 2019

In this article we explore a possible scenario of space colonization and its consequences for planet Earth. We argue that in the short term space colonization will take place, but not in the form often presented in scientific and science fiction literature. Space colonies will be fully automated. There are three main reasons to believe that this is...

The unique nature of microgravity encountered in space provides an opportunity for drug discovery and development that cannot be replicated on Earth. From the production of superior protein crystals to the identification and validation of new drug targets to microarray analyses of transcripts attenuated by microgravity, there are numerous examples...

The development and deployment of artificial intelligence (AI) is and will profoundly reshape human society, the culture and the composition of civilisations which make up human kind. All technological triggers tend to drive a hype curve which over time is realised by an output which is often unexpected, taking both pessimistic and optimistic persp...

Introduction Tralokinumab is a monoclonal antibody (mAb) that neutralizes interleukin (IL)-13, a cytokine involved in the pathogenesis of asthma. Objective The objectives of this study were to characterize the potential immunogenic properties of tralokinumab and report data for anti-drug antibodies (ADAs) and hypersensitivity reactions from two ph...

The article explains the possible options the human species has for near and deep space travel and colonisation. It makes the presumption that mankind is undergoing the Holocene extinction level event at that the need for settlement of our species beyond Earth may be more than scientific curiosity alone but an essential step in preserving our exist...

It is widely accepted that astronauts living in space undergo many physical and psychological challenges as a consequence of being in microgravity. The ergonomics of living in microgravity demands countermeasures and mitigation strategies which today and in part, are delivered by undergoing defined, rigorous exercise regimes. On the International S...

Background: The role of interleukin 13 in airway inflammation and remodelling in asthma is unclear. Tralokinumab is a human monoclonal antibody that neutralises interleukin 13. We aimed to evaluate whether tralokinumab would have an effect on airway eosinophilic infiltration, blood and sputum eosinophil concentrations, eosinophil activation, and a...

Objective: Rheumatoid arthritis (RA) is a chronic, autoimmune and degenerative joint disease leading to disability, reduced life quality, and increased mortality. Although several synthetic and biological disease modifying anti-rheumatic drugs (DMARDs) are available, there is still a medical need for novel drugs controlling disease progression. As...

Tralokinumab, a fully human IgG4monoclonal antibody, specifically neutralizes IL-13. The ATMOSPHERE clinical development program comprised four randomized, placebo-controlled clinical trials and an open-label study that aimed to assess the efficacy and safety of tralokinumab for the treatment of severe, uncontrolled asthma. The two pivotal trials (...

This article reviews some of the many challenges facing astronauts for deep space travel.

Editorial During periods of space travel, astronauts live in microgravity (MG) which has long been known to have deleterious effects on human physiology and may have psychological consequences [1]. As humans attempt to further explore the solar system, the duration of space voyages will increase and the risk to astronaut health must be protected by...

IntroductionInterleukin-13 and interleukin-4 are type-II cytokines signalling through the shared type II interleukin-4 receptor. As a result of their structural similarity, interleukin-13 and interleukin-4 have overlapping functions in the mediation of type-II-driven diseases and are, therefore, promising targets of biologic drugs currently in deve...

A short synopsis of the Fermi Paradox and possible explanations.

A mini-review summarising some of the latest research supporting the International Roadmap for artificial gravity research.

Engaging in and enduring space travel renders the human body exposed to a wide variety of acute and chronic stimuli which may necessitate pharmacological intervention. Such ergonomic challenges have led to coping and mitigation strategies and from the pioneering days of space travel in the 1950s to the current day, medications have been made availa...

Introduction: The outcome of a comparative efficacy and safety of vasoconstrictor therapies for treatment of patients with type 1 hepatorenal syndrome (HRS-1) remain inconclusive. Areas covered: We searched literature databases for randomized controlled trials (RCTs) until 31 Jan 2016, and included ten eligible RCTs. In conclusion, terlipressin wa...

Background and aim: Upper gastrointestinal bleeding (UGIB) is a complication with a high mortality rate in critically ill patients presenting with cirrhosis. Today, there exist few accurate scoring models specifically designed for mortality risk assessment in critically ill cirrhotic patients with upper gastrointestinal bleeding (CICGIB). Our aim...

Gabriela Kucharska's, project is "Logistics for Surveying conditions on Neptune" and this is what she has to say about the Aspiring STEM Leaders programme and the opportunity to work towards a Gold CREST award: "Doing the CREST project allowed me to explore areas of science that we wouldn't cover at school, areas that really intrigue me! With a hel...

Background and aim: Critically ill cirrhosis patients have an increased risk of morbidity and mortality, even after admission to the ICU. Our objectives were to compare the predictive accuracy of model for end-stage liver disease (MELD), MELD-Na, UK model for end-stage liver disease, and chronic liver failure-sequential organ failure assessment (C...

Objectives The relationship between normal low-density lipoprotein cholesterol (LDL-c) levels and non-alcoholic fatty liver disease (NAFLD) in non-obese individuals remains unclear. We aimed to investigate the precise prevalence and incidence of NAFLD within the normal LDL-c range in non-obese individuals. Design Cross-sectional and longitudinal s...

Minimal Data Set. (XLSX)

STARD Checklist. (DOCX)

Background and aims: Recently, glucose variability (GV) has been reported as an independent risk factor for mortality in non-diabetic critically ill patients. However, GV is not incorporated in any severity scoring system for critically ill patients currently. The aim of this study was to establish and validate a modified Simplified Acute Physiolo...

At present, there is no ideal model for predicting the short-term outcome of patients with acute-on-chronic hepatitis B liver failure (ACHBLF). This study aimed to establish and validate a prognostic model by using the classification and regression tree (CART) analysis. A total of 1047 patients from two separate medical centres with suspected ACHBL...

Antidiabetic medication may modify the incidence of hepatocellular carcinoma (HCC). We aimed to compare the use of different antidiabetic strategies and the incidence of HCC. PubMed, Embase.com and Cochrane Library databases were searched up to 31 October 2015 and randomized controlled trials (RCTs), cohort studies or case-control studies were incl...

Nanomedicines and nanopharmacology is a rapidly developing and evolving field with new techniques and applications under constant development. This book will provide an overview of the chemistry of nanocarrier design and the considerations that need to be made when developing a nanomedicine. Providing an understanding of the relationship of nanocar...

ABSTRACT Introduction: The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is obser...

Objectives: Recent studies suggest that an elevated preoperative platelet to lymphocyte ratio (PLR) may be considered a poor prognostic biomarker in patients with colorectal cancer (CRC). The aim of this study was to evaluate the prognostic impact of PLR in patients with CRC. Methods: We enrolled 1314 patients who underwent surgery for CRC betwe...

Introduction: Toll-like receptors (TLRs) are expressed by a wide variety of cell types including immune cells. They play a crucial role in the inflammatory and host defense response against microorganisms, and triggering TLRs can mediate the activation of innate immunity. Furthermore, research suggests that various TLRs may function differently on...

Objectives: To evaluate the association between sex-specific serum high sensitive C reactive protein (hsCRP) levels and NAFLD in a large population-based study. Results: From Q1 to Q4, the incidence ratios were 21.1 (95% CI 17.5 24.7), 18.6 (95% CI 16.5 20.8), 24.8 (95% CI 22.4 27.2) and 31.1 (95% CI 28.5 33.6) in males and 6.2 (95% CI 4.4 8.0),...

Macrophages in the arterial intima sustain chronic inflammation during atherogenesis. Under hypercholesterolemic conditions murine Ly6Chigh monocytes surge in the blood and spleen, infiltrate nascent atherosclerotic plaques, and differentiate into macrophages that proliferate locally as disease progresses. Spleen tyrosine kinase (SYK) may participa...

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and the novel systemic inflammation marker platelet-to-lymphocyte ratio (PLR) may be associated with clinical outcome in patients with DKA. This study aimed to investigate the utility of PLR in predicting 90-day clinical outcomes in patients with DKA. Patient...

Objectives: Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD. Methods: A total of 60527...

Hypersensitivity reactions can be elicited by various factors: either immunologically induced, i.e., allergic reactions to natural or synthetic compounds mediated by IgE, or non-immunologically induced, i.e., activation of mediator release from cells through direct contact, without the induction of, or the mediation through immune responses. Mediat...

Multifactorial causes can lead to osteoarthritis (OA), and its pathogenesis is not clearly understood yet (Berenbaum 2013; Santos et al. 2014; Liu-Bryan and Terkeltaub 2015). The main characteristics of OA are the slowly progressing deterioration of the articular cartilage, accompanied by intermitted painful inflammatory episodes, and a continuous...

Objectives: Neutrophil lymphocyte ratio (NLR) has been shown to predict prognosis of cancers in several studies. This study was designed to evaluate the impact of stratified NLR in patients who have received curative liver resection (CLR) for hepatocellular carcinoma (HCC). Methods: A total of 1659 patients who underwent CLR for suspected HCC be...

Objective: A key goal in gout treatment is achieving sustained serum uric acid (sUA) lowering. Point-of-care test (PoCT) meters provide convenient, rapid measures of sUA levels to monitor/adjust therapy. Four commercially available sUA PoCT meters were compared qualitatively (ease of use) and quantitatively (precision/accuracy). Methods: Liquid...

The prevalence of end-stage renal disease is emerging as a serious worldwide public health problem because of the shortage of donor organs and the need to take lifelong immunosuppressive medication in patients who receive a transplanted kidney. Recently, tissue bioengineering of decellularization and recellularization scaffolds has emerged as a nov...

Long non-coding RNA (lncRNA) is commonly defined as an RNA with a length of greater than 200 nucleotides, frequently up to 100 kb. Numerous studies have shown that dysregulation of lncRNAs may directly relate to a number of human diseases, particularly in oncology where lncRNAs appear to play an important role. LncRNAs may also play a potentially n...

Methimazole is commonly prescribed for patients who are thyrotoxic. Cholestatic hepatitis is a rare but serious adverse event which may be associated with interventional therapy. In this case report, we present two Chinese women with cholestatic jaundice due to methimazole treatment. Both patients had a history of hyperthyroidism; initial laborator...

Off-target pharmacology may contribute to both adverse and beneficial effects of a new drug. In vitro pharmacological profiling is often applied early in drug discovery; there are fewer reports addressing the relevance of broad profiles to clinical adverse effects. Here, we have characterized the pharmacological profile of the active metabolite of...

Fostamatinib is a tyrosine kinase inhibitor with activity against spleen tyrosine kinase which has completed clinical trials for patients with rheumatoid arthritis. In clinical studies fostamatinib treatment was associated with a small elevation of systemic arterial blood pressure (BP), a similar finding to that seen with other kinase inhibitors, e...

Introduction: Nonalcoholic fatty liver disease (NAFLD) is a major, worldwide public health problem. NAFLD is recognized as a major cause of liver-related morbidity and mortality. However, physicians are currently limited by available treatment options. Recently, numerous studies have reported a correlation between serum uric acid (SUA) and NAFLD w...

Objectives: Therapies for treatment of patients with primary sclerosing cholangitis (PSC) include administration of ursodeoxycholic acid (UDCA) alone, or combination with metronidazole (MTZ) or mycophenolate mofetil (MMF), respectively. However, the optimum regimen still remains inconclusive. We aimed to compare interventions in terms of patient m...

Eosinophils are key effector cells in asthma-associated airway inflammation and remodeling; IL-13 is involved in regulating eosinophil activity. Tralokinumab, currently in Phase III clinical development for patients with severe uncontrolled asthma, is an investigational fully human monoclonal antibody designed to inhibit IL-13. In Phase II studies,...

In a Phase IIb study, administration of tralokinumab, an anti-IL-13, fully human monoclonal antibody, to patients with severe uncontrolled asthma treated with high-dose inhaled corticosteroid (ICS) and long-acting β2-agonists (LABA) significantly improved lung function. Since many patients with severe asthma using ICS-LABA only achieve symptom cont...

R406 solubility in a range of buffers. Table S2. Full in vitro pharmacological profile of R406. Table S3. Full in vitro kinase profile of R406.

Introduction: The effects of the anti-IL-13 monoclonal antibody tralokinumab (tralo) (CAT-354) on airway dimensions were assessed in a subgroup of subjects from a Phase 2b study. Methods: In a 52-week double-blind study (NCT01402986) adults with severe asthma (history of airway reversibility, ≥2 exacerbations in previous year and FEV1 40–80% predic...

Ethanol metabolism in hepatocytes causes the generation of reactive oxygen species, endoplasmic reticulum stress and alterations in mitochondrial energy and REDOX metabolism. In ethanol-exposed liver disease, autophagy not only acts as a cleanser to remove damaged organelles and cytosolic components, but also selectively clears specific targets suc...