Blue Arabia : Palaeolithic and Underwater Survey in SW Saudi Arabia and the Role of Coasts in Pleistocene Dispersal

The role of coastal regions and coastlines in the dispersal of human populations from Africa and across the globe has been highlighted by the recent polarisation between coastal and interior models. The debate has been clouded by the use of the single term ‘coastal dispersal’ to embrace what is in fact a wide spectrum of possibilities, ranging from seafaring populations who spend most of their time at sea living off marine resources, to land-based populations in coastal regions with little or no reliance on marine foods. An additional complicating factor is the fact of Pleistocene and early Holocene sea-level change, which exposed an extensive coastal region that is now submerged, and may have afforded very different conditions from the modern coastal environment. We examine these factors in the Arabian context and use the term ‘Blue’ to draw attention to the fertile coastal rim of the Arabian Peninsula, and to the now submerged offshore landscape, which is especially extensive in some regions. We further emphasise that the attractions of the coastal rim are a product of two quite different factors, ecological diversity and abundant water on land, which have created persistently ‘Green’ conditions throughout the vagaries of Pleistocene climate change in some coastal regions, especially along parts of the western Arabian escarpment, and potentially productive marine environments around its coastline, which include some of the most fertile in the world. We examine the interplay of these factors in the Southwest region of Saudi Arabia and the southern Red Sea, and summarise some of the results of recent DISPERSE field investigations, including survey for Palaeolithic sites on the mainland, and underwater survey of the continental shelf in the vicinity of the Farasan Islands. We conclude that coastlines are neither uniformly attractive nor uniformly marginal to human dispersal, that they offer diverse opportunities that were spatially and temporally variable at scales from the local to the continental, and that investigating Blue Arabia in relation to its episodically Green interior is a key factor in the fuller understanding of long-term human population dynamics within Arabia and their global implications

Direct Measurement of Supra-Physiological Levels of Ascorbate in Plasma using a Nanophotometer

High dose intravenously administered vitamin C (ascorbate) is currently being tested in clinical trials as an adjuvant to current standard of care therapies in a variety of cancers. Intravenous infusion is used with a goal to achieve supraphysiological ascorbate concentrations in blood of at least 20 mM, 300 to 500 times normal healthy concentrations (0.04-0.08 mM). These trials need quick and easy access to information on the levels of ascorbate achieved in the blood to make clinical decisions. Previous methods that quantify ascorbate levels in blood require extensive preparation, time, and materials that may not always be present in clinical settings. We developed a new approach to meet this need using direct UV spectroscopy with a nanophotometer. The only preparation required is centrifugation of whole blood to separate the red blood cells from plasma. No more than 3 microliters of plasma are needed; the approach can determine the concentration of ascorbate in the range of 3 – 35 mM; the method is fast and efficient. This approach has already been deployed to gather this information in a clinical trial with lung cancer patients

A randomised controlled trial of small particle inhaled steroids in refractory eosinophilic asthma (SPIRA)

Background: Some patients with refractory asthma have evidence of uncontrolled eosinophilic inflammation in the distal airways. While traditional formulations of inhaled steroids settle predominantly in the large airways, newer formulations with an extra-fine particle size have a more peripheral pattern of deposition. Specifically treating distal airway inflammation may improve asthma control. Methods: 30 patients with refractory asthma despite high dose inhaled corticosteroids were identified as having persistent airway eosinophilia. Following 2 weeks of prednisolone 30 mg, patients demonstrating an improvement in asthma control were randomised to receive either ciclesonide 320 µg twice daily or placebo in addition to usual maintenance therapy for 8 weeks. The primary outcome measure was sputum eosinophil count at week 8. Alveolar nitric oxide was measured as a marker of distal airway inflammation. Results: There was continued suppression of differential sputum eosinophil counts with ciclesonide (median 2.3%) but not placebo (median 4.5%) though the between-group difference was not significant. When patients who had changed their maintenance prednisolone dose during the trial were excluded the difference between groups was significant (1.4% vs 4.5%, p=0.028). Though alveolar nitric oxide decreased with ciclesonide the value did not reach statistical significance. Conclusions: These data demonstrate that patients with ongoing eosinophilic inflammation are not truly refractory, and that suppression of airway eosinophilia may be maintained with additional inhaled corticosteroid. Further work is needed with a focus on patient-orientated outcome measures such as exacerbation rate, with additional tests of small airway function. Trial registration number NCT01171365. Protocol available at http://www.clinicaltrials.gov

Interventions to increase physical activity and reduce sedentary behaviour in severe mental ill health: How effective are they?’- A systematic review.

Background People with severe mental ill health experience a mortality gap of 15–20 years and one of the main reasons for this is due to preventable physical health conditions. Physical activity can reduce the risk of developing physical health conditions such as diabetes and cardiovascular disease yet people with severe mental ill health are less physically active and more sedentary than the general population. Methods A systematic review was conducted to investigate the effectiveness of interventions aimed at increasing physical activity and reducing sedentary behaviour in people with severe mental ill health. The protocol was published with PROSPERO (CRD42021277579). Randomised controlled trials conducted in any country in any setting and published in English with an aim of increasing physical activity or reducing sedentary behaviour were included. Results Eleven unique studies were identified for inclusion. Due to the variability between interventions, outcome measures, and time points, it was not possible to conduct a meta-analysis. Effect estimates suggested that three of the interventions were effective at increasing physical activity. However, the certainty of the evidence was rated as low using the GRADE approach. Conclusions The evidence on interventions to increase activity shows promise but is insufficiently robust for an intervention to be recommended in clinical guidelines. More high-quality and statistically powered trials are needed to guide best practice and policy

Physical activity in adults with schizophrenia and bipolar disorder: a large cross-sectional survey exploring patterns, preferences, barriers, and motivating factors

Adults with severe mental ill health may have specific attitudes toward physical activity. To inform intervention development, we conducted a survey to assess the physical activity patterns, preferences, barriers, and motivations of adults with severe mental ill health living in the community. Data were summarised using descriptive statistics, and logistic regressions were used to explore relationships between physical activity status and participant characteristics. Five-hundred and twenty-nine participants (58% male, mean age 49.3 years) completed the survey. Large numbers were insufficiently active and excessively sedentary. Self-reported levels of physical activity below that recommended in national guidelines were associated with professional inactivity, consumption of fewer than five portions of fruit and vegetables per day, older age, and poor mental health. Participants indicated a preference for low-intensity activities and physical activity that they can do on their own, at their own time and pace, and close to home. The most commonly endorsed source of support was social support from family and friends. Common motivations included improving mental health, physical fitness, and energy levels. However, poor mental and physical health and being too tired were also common barriers. These findings can inform the development of physical activity interventions for this group of people

Structure of a Nudix hydrolase (MutT) in the Mg2+-­bound state from Bartonella henselae, the bacterium responsible for cat scratch fever

B. henselae is the etiological agent responsible for cat scratch fever (bartonellosis). The crystal structure of the smaller of the two Nudix hydrolases encoded in the genome of B. henselae, Bh-MutT, was determined to 2.1 Å resolution

Hidden in the Middle : Culture, Value and Reward in Bioinformatics

Bioinformatics - the so-called shotgun marriage between biology and computer science - is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised 'outputs' in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the 'parent' disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether

Supporting physical activity through co-production in people with severe mental ill health (SPACES): protocol for a randomised controlled feasibility trial.

Background Severe mental ill health (SMI) includes schizophrenia, bipolar disorder and schizoaffective disorder and is associated with premature deaths when compared to people without SMI. Over 70% of those deaths are attributed to preventable health conditions, which have the potential to be positively affected by the adoption of healthy behaviours, such as physical activity. People with SMI are generally less active than those without and face unique barriers to being physically active. Physical activity interventions for those with SMI demonstrate promise, however, there are important questions remaining about the potential feasibility and acceptability of a physical activity intervention embedded within existing NHS pathways. Method This is a two-arm multi-site randomised controlled feasibility trial, assessing the feasibility and acceptability of a co-produced physical activity intervention for a full-scale trial across geographically dispersed NHS mental health trusts in England. Participants will be randomly allocated via block, 1:1 randomisation, into either the intervention arm or the usual care arm. The usual care arm will continue to receive usual care throughout the trial, whilst the intervention arm will receive usual care plus the offer of a weekly, 18-week, physical activity intervention comprising walking and indoor activity sessions and community taster sessions. Another main component of the intervention includes one-to-one support. The primary outcome is to investigate the feasibility and acceptability of the intervention and to scale it up to a full-scale trial, using a short proforma provided to all intervention participants at follow-up, qualitative interviews with approximately 15 intervention participants and 5 interventions delivery staff, and data on intervention uptake, attendance, and attrition. Usual care data will also include recruitment and follow-up retention. Secondary outcome measures include physical activity and sedentary behaviours, body mass index, depression, anxiety, health-related quality of life, healthcare resource use, and adverse events. Outcome measures will be taken at baseline, three, and six-months post randomisation. Discussion This study will determine if the physical activity intervention is feasible and acceptable to both participants receiving the intervention and NHS staff who deliver it. Results will inform the design of a larger randomised controlled trial assessing the clinical and cost effectiveness of the intervention. Trial registration ISRCTN: ISRCTN83877229. Registered on 09.09.2022

Genomic epidemiology reveals multiple introductions of Zika virus into the United States

Zika virus (ZIKV) is causing an unprecedented epidemic linked to severe congenital abnormalities. In July 2016, mosquito-borne ZIKV transmission was reported in the continental United States; since then, hundreds of locally acquired infections have been reported in Florida. To gain insights into the timing, source, and likely route(s) of ZIKV introduction, we tracked the virus from its first detection in Florida by sequencing ZIKV genomes from infected patients and Aedes aegypti mosquitoes. We show that at least 4 introductions, but potentially as many as 40, contributed to the outbreak in Florida and that local transmission is likely to have started in the spring of 2016-several months before its initial detection. By analysing surveillance and genetic data, we show that ZIKV moved among transmission zones in Miami. Our analyses show that most introductions were linked to the Caribbean, a finding corroborated by the high incidence rates and traffic volumes from the region into the Miami area. Our study provides an understanding of how ZIKV initiates transmission in new regions